Ca<sup>2+</sup>/Calmodulin and Presynaptic Short-Term Plasticity

Mochida, Sumiko

doi:https://doi.org/10.5402/2011/919043

International Scholarly Research Notices

On this page

Abstract Introduction Conclusion References Copyright Related Articles

Review Article | Open Access

Volume 2011 | Article ID 919043 | https://doi.org/10.5402/2011/919043

Ca²⁺/Calmodulin and Presynaptic Short-Term Plasticity

Sumiko Mochida¹

Academic Editor: L. Srivastava, F. G. Wouterlood

Received22 Mar 2011

Accepted18 Apr 2011

Published23 Jun 2011

Abstract

Synaptic efficacy is remodeled by neuronal firing activity at the presynaptic terminal. Presynaptic activity-dependent changes in transmitter release induce postsynaptic plasticity, including morphological change in spine, gene transcription, and protein synthesis and trafficking. The presynaptic transmitter release is triggered and regulated by Ca²⁺, which enters through voltage-gated Ca²⁺ (Ca_V) channels and diffuses into the presynaptic terminal accompanying action potential firings. Residual Ca²⁺ is sensed by Ca²⁺-binding proteins, among other potential actions, it mediates time- and space-dependent synaptic facilitation and depression via effects on Ca_V2 channel gating and vesicle replenishment in the readily releasable pool (RRP). Calmodulin, a Ca²⁺-sensor protein with an EF-hand motif that binds Ca²⁺, interacts with Ca_V2 channels and autoreceptors in modulation of SNARE-mediated exocytosis.

1. Introduction

For memory formation in a neuronal circuit, the primary function of presynaptic terminals is the firing activity-dependent release of neurotransmitters and subsequent recycling of their carrier synaptic vesicles, processes which critically depend on ATP and Ca²⁺. Presynaptic firing of action potentials activates voltage-gated Ca²⁺ (Ca_V) channels, and Ca²⁺ entry initiates release of neurotransmitters. Ca²⁺ dependence on fast neurotransmitter release is thought to be conferred by the synaptotagmin, a family of Ca²⁺ sensors that interact with SNAREs [1]. Synaptotagmin 1 and 2 are synaptic vesicle proteins with tandem C2 domains that bind Ca²⁺ and ensure the synchronization of Ca²⁺-dependent exocytosis with the presynaptic action potential [2–5]. Neuronal firing activity also controls other protein functions and dynamically remodels synaptic efficacy. Ca²⁺-binding proteins sensing residual Ca²⁺, which accumulates locally in the presynaptic terminal during trains of action potentials, may act as potential effectors for these reactions. Considerable evidence supports a role for calmodulin (CaM), another family of Ca²⁺ sensors with an EF hand motif that binds Ca²⁺, in modulation of SNARE-mediated exocytosis [6, 7] and endocytosis [8, 9]. Targets of CaM include multiple proteins implicated in exocytosis (e.g., Ca²⁺ channels [10], Ca²⁺/ CaM kinase II [11], rab3 [12], and Munc13 [13]), and endocytosis (e.g., calcinulin [14]). Another Ca²⁺-binding protein with an EF hand motif, parvalbumin, acts as a mobile presynaptic Ca²⁺ buffer that accelerates withdrawal of residual Ca²⁺ and decay of short-term facilitation in the calyx of held [15] and GABAergic synapses between interneurons and Purkinje cells [16]. Calretinin is upregulated in the calyx of held during postnatal development and may act as a Ca²⁺ effector or Ca²⁺ buffer to regulate transmitter release probability [17].

A large number of proteins are involved in presynaptic function; their synthesis, transport, and function appear to be regulated by presynaptic firing activity [18–20], Sympathetic superior cervical ganglion (SCG) neurons, which form a well-characterized cholinergic synapse in long-term culture [21, 22], are an ideal cell model [21, 23] with which to investigate these processes. The SCG neuron has a large cell body and nucleus that allows for the manipulation of gene expression and function in mature neurons via acute microinjection of cDNA, small interfering RNA (siRNA), dominant-negative transgenes, peptides, antibodies, and metabolites [21, 24–27], an approach not technically feasible for cultured neurons from the central nervous system. In addition, synaptic activity and short-term plasticity, as it relates to the size and replenishment of functional synaptic vesicle pools, can be accurately monitored by recording excitatory postsynaptic potentials (EPSPs) evoked by paired or repetitive action potentials in presynaptic neurons. Using this approach, we recently uncovered a critical role for CaM in presynaptic short-term plasticity [26, 28]. Our new findings concerning activity-dependent regulation of synaptic efficacy by modulating synaptic vesicle exocytosis which underlies memory formation in the brain are summarized in this paper. CaM is a Ca²⁺ effector sensing residual Ca²⁺ that mediates time- and space-dependent synaptic depression and facilitation via effects on Ca_V2 channel gating [26] and vesicle replenishment in the readily releasable pool (RRP) [28]. To maintain synaptic remodeling, mitochondrial ATP biogenesis supports synaptic transmission, including efficient mobilization of synaptic vesicles into the RRP for the generation of short-term plasticity [29].

2. Ca_V2.1 Channel Regulation and Short-Term Plasticity

2.1. Ca²⁺/CaM Modulates CaV2.1 Channel Activity

At most fast synapses in the central nervous system, Ca_V2.1 channels are densely clustered [30], and Ca²⁺ entered through Ca_V2.1 channels initiates synaptic transmission [31, 32]. Ca_V2.1 channels are Ca²⁺-dependently regulated by CaM [10, 33–36] and related to neuron-specific Ca²⁺-binding proteins, calcium-binding protein 1 and visinin-like protein-2 [37–39]. CaM and the Ca²⁺-binding proteins interact with a bipartite regulatory site in the intracellular C terminus of the α₁2.1 subunit [36] called the IQ-like motif, which begins with the sequence isoleucine-methionine (IM) rather than isoleucine-glutamine (IQ); they also interact with the nearby downstream CaM-binding site. Alanine substitutions in the IQ-like domain (α₁2.1_IM-AA) blocked Ca²⁺-dependent facilitation of Ca_V2.1 channels [34, 36], whereas Ca²⁺-dependent inactivation was blocked in channels lacking the adjacent CaM-binding domain (CBD; α₁2.1_ΔCBD) [10, 35, 36, 38, 39].

Ca²⁺/CaM-dependent inactivation of Ca_V2.1 channels is dependent on global elevations of Ca²⁺ [35], which in turn are dependent on the density of Ca²⁺ channels, local Ca²⁺ buffers, the volume of the intracellular compartment, and other differences in the cellular context in which the channels are located. Ca²⁺-dependent inactivation of Ca_V2.1 channels is observed in transfected cells overexpressing Ca_V2.1 channels [10, 34, 35] and in the nerve terminals of the calyx of Held [40, 41], where Ca_V2.1 channels are densely localized and large Ca²⁺ transients are generated. In contrast, Ca²⁺-dependent inactivation is not reliably observed in the large neuronal cell bodies of Purkinje neurons [42] or SCG neurons [26].

2.2. Ca²⁺/CaM-Mediated Ca_V2.1 Channel Modulation, Synaptic Facilitation and Depression

Paired-pulse facilitation (PPF) and paired-pulse depression (PPD) are both mediated by Ca²⁺/CaM-dependent regulation of Ca_V2.1 channels [26]. EPSPs recorded by pairs of action potentials with varied stimulation intervals show PPD and PPF in synaptically connected SCG neurons in which the presynaptic neuron was transfected with the α₁2.1_WT. PPD with short interstimulus interval (<40 ms) was blocked by the α₁2.1_ΔCBD transfection, while PPF with intermediate interstimulus interval (50–100 ms) was blocked by the α₁2.1_IM-AAtransfection. Thus, temporal regulation of Ca_V2.1 channels contributes to PPD and PPF by changing the release probability in an activity-dependent manner in response to Ca²⁺ entry during the first action potential of the pair, suggesting a spatial change in Ca²⁺ concentration at the active zone and also regulates Ca_V2.1 channel activity.

Neural information is encoded in bursts of synaptic activity in vivo. During bursts of action potentials, the CaM-dependent regulation of Ca_V2.1 is involved in the short-term synaptic plasticity (Figure 1). Repetitive stimulation produces frequency-dependent regulation of EPSPs in SCG neurons. As the frequency of stimulation was increased, synaptic transmission mediated by the α₁2.1_WT showed increased facilitation followed by depression during the trains of 1 s (Figure 1(a), WT). This form of short-term synaptic plasticity resembles that recorded at the calyx of Held in response to repetitive stimuli [40, 41, 43]. The facilitation is reduced by the IM-AA mutation (Figure 1(a), IM-AA) but not by the ∆CBD mutation (Figure 1(a), ∆CBD), suggesting that enhancement of neurotransmission following 1 s trains requires CaM binding to the IQ-like domain. In contrast to the facilitation followed by depression of synaptic transmission observed during trains for WT, the EPSP size increased steadily during trains (<30 Hz) for ∆CBD (Figure 1(a), ΔCBD). Facilitation of the ΔCBD mutant was greater than the WT and the IM-AA mutant throughout the train, and depression was much slower, suggesting that, similar to paired-pulse experiments, CaM-dependent inactivation of Ca_V2.1 channels shapes the time course of short-term synaptic plasticity by determining the timing of the peak of synaptic facilitation during the train as well as the steady-state level of synaptic depression at the end of the train.

Figure 1

Presynaptic facilitation and depression mediated by Ca_V2.1 channel facilitation and inactivation. (a) Averaged trace of EPSPs (), in which Ca_V2.1 channels were the only active channels in the presence of ω-conotoxin GVIA, evoked by action potentials with 1 s train at 30 Hz. (b) Normalized amplitudes of EPSPs recorded every 2 s in the presence of ω-Conotoxin GVIA. Conditioning stimuli were applied at the indicated times at 20 Hz for 10 s to evoke augmentation and at 20 Hz for 60 s to induce PTP. Adapted from Mochida et al., 2008 [26]. (c) Model illustrating Ca_V2.1-mediated mechanisms of synaptic depression, facilitation, and augmentation. In synaptic depression, CaM sensing local Ca²⁺ interacts with the CaM-binding domain (CBD) to cause channel inactivation and reduce Ca²⁺ entry, thus, reducing neurotransmitter release. In synaptic facilitation and augmentation, CaM sensing global Ca²⁺ interacts with the IQ-like motif to cause channel facilitation and increase in Ca²⁺ entry, and subsequently neurotransmitter release increases.

Two forms of presynaptic short-term enhancement of synaptic transmission, termed augmentation and posttetanic potentiation (PTP), last for seconds to minutes [44]. In SCG neurons, augmentation is elicited with 10 s trains [45], and PTP is elicited with 60 s trains [46, 47]. Augmentation observed with 10 Hz, 20 Hz, and 40 Hz trains is significantly reduced by the IM-AA mutation, whereas the ΔCBD mutation has little effect on the magnitude of the augmentation [26]. Thus, Ca²⁺/CaM-dependent facilitation of Ca²⁺ entry significantly contributes to an intermediate-length form of synaptic enhancement and augmentation, which has a time course of tens to hundreds of milliseconds [26]. In contrast to augmentation, the Ca²⁺ signal that induces PTP does not require Ca²⁺/CaM-dependent facilitation. Consistent with this idea, previous reports suggested that PTP, but not augmentation, resulted from the slow efflux of mitochondrial Ca²⁺ accumulated during titanic stimulation [48] and also involved activation of protein kinase C [49, 50].

2.3. Ca²⁺/CaM-Mediated CaV2.1 Channel Modulation and Presynaptic Short-Term Plasticity

Short-term synaptic plasticity is crucial for encoding information in the nervous system [51]. Changes in the concentration of residual Ca²⁺ are temporally sensed by a Ca²⁺ sensor CaM, resulting in Ca²⁺-dependent facilitation and inactivation of presynaptic Ca_V2.1 currents. These currents can mediate short-term synaptic facilitation and depression, which are conserved forms of plasticity at many different types of synapses [44]. Evidently, by causing facilitation and inactivation of Ca_V2.1 channels, residual Ca²⁺ can actually control “instantaneous” Ca²⁺ during an action potential, shape the local Ca²⁺ transient at the active zone, and cause facilitation, augmentation, and depression of synaptic transmission. The postsynaptic response is, therefore, controlled by Ca²⁺/CaM-dependent modulation of presynaptic Ca²⁺ entry, which acts to encode the information contained in the frequency of presynaptic firing of action potentials for transmission to the postsynaptic cell. Thus, presynaptic Ca²⁺ channel regulation by CaM is a major molecular mechanism underlying information processing in the nervous system.

3. CaM, mGluR and Munc 18-1 Interaction and Synaptic Facilitation

3.1. Presynaptic mGluRs

Presynaptic group III metabotropic glutamate receptors (mGluR4, mGluR7, and mGluR8) are expressed in the presynaptic active zone and reduce synaptic vesicle release upon stimulation by agonists [52–55]. A prominent enigma concerning the function of group III mGluRs is depicted in the case of mGluR4: short-term synaptic facilitation is impaired in mGluR4-KO mice although the expression of the plasticity is not reduced by pharmacological blockade of mGluR4 [52, 56]. These findings suggest the existence of some ligand-independent functions of the receptor linked to synaptic vesicle release [52]. It has been shown that Ca²⁺-dependent CaM binds to the intracellular C-terminal tail (ct) of group III mGluRs [28, 57]. Because the affinity of CaM for Ca²⁺ [58] corresponds to the required residual Ca²⁺ level for the expression of short-term facilitation, a molecule that can bind to the ct region of group III mGluRs and have an interaction with the receptor that is regulated by Ca²⁺-activated CaM is a good candidate for mGluR-mediated expression of short-term synaptic facilitation.

3.2. CaM and Munc18-1 Interactions with Presynaptic mGluRs

Munc18-1 is a protein essential for neurotransmission [59] and promotes SNAREs-mediated vesicle fusion [60]. Coimmunoprecipitation and in vitro binding experiments indicated that either mGluR4 or mGluR7 directly interacted with Munc18-1 in the brain. Group II mGluRs are also expressed presynaptically and modulate synaptic transmission [53–55]. However, group II mGluRs are localized in the preterminal portions of axons but not in the active zone [55] and do not interact with Munc18-1. Munc18-1 can be divided into three domains [61]; it binds to ct-mGluR4 through domain 1 [28].

CaM binds to the membrane-proximal region of group III ct-mGluRs [57, 62]. Munc18-1 binds to this region of ct-mGluR4; the interaction is disrupted by Ca²⁺-activated CaM at a concentration of residual Ca²⁺ [44]. Although Munc18-1 does not have an apparent Ca²⁺-binding motif, the interaction between ct-mGluR4 and Munc18-1 is enhanced with increasing concentrations of Ca²⁺, with saturation at 3 μM. In the presence of CaM, mGluR4 binds Munc18-1 at the resting Ca²⁺ level of 0.1 μM and releases it above the Ca²⁺ level of 1 μM, corresponding to the residual Ca²⁺ level after an action potential.

3.3. mGluR4-Mediated Regulation of Basal Transmitter Release and Synaptic Facilitation

Function of the mGluR4/Munc18-1 interaction in synaptic transmission is the reduction of basal transmitter release [28]. At synapses of cultured SCG neurons, where mGluR4 is not expressed [63], the injection of mGluR4 peptide, residues 849–889, reduced gradually the amplitude of EPSPs. The time course and extent of inhibition were similar to that caused by the injection of the domain 1 of Munc18-1, suggesting that the mGluR4/Munc18-1 interaction is inhibitory to synaptic transmission.

Generally, a decrease in the initial probability of transmitter release leads to a larger synaptic enhancement or a reduction of synaptic depression [44, 64]. From the above inhibitory role of mGluR4 peptide in synaptic transmission and the operating range of the Ca²⁺-sensing mechanism, mGluR4C appears to be responsible for the expression of short-term synaptic facilitation; at the very least it reduces short-term synaptic depression. Acutely, PPD, but not PPF, was suppressed in the presence of mGluR4C peptide, suggesting that mGluR4 peptide introduces a facilitating property to these synapses which is apparent when these synapses exhibit PPD. This evidence is consistent with the idea that the absence in the ct region of mGluR4 accounts for the impaired expression of PPF in mGluR4-KO mice [56].

3.4. The Role of Ca²⁺/CaM, Munc18, and mGluR Interactions in Activity-Dependent Synaptic Transmission

An accumulation of evidence suggests a model for the mGluR4/Munc18-1 interaction in the regulation of synaptic transmission in the brain. When neurons are inactive, Munc18-1 is sequestered by mGluR4; therefore, basal synaptic transmission is kept low. After the action potential, residual Ca²⁺ activates CaM, which in turn liberates Munc18-1 from mGluR4, causing short-term synaptic facilitation (Figure 2). This Ca²⁺-sensing mechanism demonstrates a function for mGluR4 in the expression of short-term facilitation and explains the discrepancy between pharmacological blockade and gene targeting of mGluR4, revealed clearly at the parallel fiber synapses onto cerebellar Purkinje cells [52, 56]. Another interesting implication of our findings is that the presence of mGluR4 is responsible for the expression of certain synaptic properties (e.g., mGluR4-positive facilitating parallel fiber synapses and mGluR4-negative depressing climbing fiber synapses onto the same cerebellar Purkinje cells [44, 51, 65]). Although Munc18-1 is known to be an essential protein for synaptic transmission, evidence for both positive and negative roles of Munc18-1 in synaptic transmission has been reported [59]. If Munc18-1 has a negative role in synaptic transmission, then our data suggests that the ct-mGluR4/Munc18-1 interaction augments the inhibitory function of Munc18-1. In this case, disruption of this negative complex by Ca²⁺/CaM would relieve Munc18-1-mediated inhibition and consequently lead to synaptic facilitation. Thus, no matter whether Munc18-1 had a positive or negative role in synaptic vesicle release, the Ca²⁺-sensing system would operate in the expression of short-term synaptic facilitation.

Figure 2

Model illustrating presynaptic short-term facilitation by Ca²⁺/CaM-mediated Munc18-1 release from mGluR4. Step 1: At the resting Ca²⁺ level, Munc18-1 is sequestered by mGluR4. Step 2: Owing to the low availability of Munc18-1 for SNARE, the initial synaptic vesicle release is small. Steps 2-3: Following the action potential, CaM sensing residual Ca²⁺ liberates Munc18-1 from mGkuR4. Step 4: The higher availability of Munc18-1 for SNARE enables a greater release of synaptic vesicles in response to the second action potential, which is derived in rapid succession. Adapted from Nakajima et al., 2009 [28].

4. Conclusion

Neuronal firing activity controls the functions of synaptic proteins and dynamically remodels synaptic efficacy. Ca²⁺-binding proteins that sense residual Ca²⁺, which temporally and spatially accumulates in the active zone during trains of action potentials, act as potential effectors for these reactions at the presynaptic terminal. Two pieces of evidence are shown in this article (Figures 1 and 2). First, CaM interacts with a bipartite regulatory site of the α₁2.1 subunit at the mouth of Ca²⁺ channels, senses firing-dependent temporal changes in local and global elevations of Ca²⁺, and regulates activity of Ca²⁺ channels for SNAREs-mediated synaptic vesicle exocytosis [33, 66]. The CaM regulation of Ca²⁺ channels results in presynaptic depression and facilitation (Figure 1). Secondly, CaM regulates synaptic efficacy by controlling the supply of Munc 18-1 at the active zone (Figure 2). Munc18-1, an essential protein for SNAREs-mediated synaptic vesicle membrane fusion [59], binds to mGluR4 in the active zone [53–55] at the resting state. With elevation of Ca²⁺, Ca²⁺/CaM binds to mGluR4 in place of Munc18-1 [57, 62]. The Ca²⁺/CaM regulation of the mGluR4/Munc18-1 interaction results in presynaptic facilitation. The presynaptic events shown here control synaptic efficacy and encode postsynaptic activity that underlie generation of the synaptic plasticity resulting in regulation of neural circuits.

References

T. C. Südhof, “The synaptic vesicle cycle,” Annual Review of Neuroscience, vol. 27, pp. 509–547, 2004.
View at: Publisher Site | Google Scholar
T. I. Nishiki and G. J. Augustine, “Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons,” Journal of Neuroscience, vol. 24, no. 27, pp. 6127–6132, 2004.
View at: Publisher Site | Google Scholar
Z. P. Pang, J. Sun, J. Rizo, A. Maximov, and T. C. Südhof, “Genetic analysis of synaptotagmin 2 in spontaneous and Ca²⁺ -triggered neurotransmitter release,” EMBO Journal, vol. 25, no. 10, pp. 2039–2050, 2006.
View at: Publisher Site | Google Scholar
J. Sun, Z. P. Pang, D. Qin, A. T. Fahim, R. Adachi, and T. C. Südhof, “A dual-Ca²⁺-sensor model for neurotransmitter release in a central synapse,” Nature, vol. 450, no. 7170, pp. 676–682, 2007.
View at: Publisher Site | Google Scholar
M. Yoshihara and J. T. Littleton, “Synaptotagmin functions as a calcium sensor to synchronize neurotransmitter release,” Neuron, vol. 36, no. 5, pp. 897–908, 2002.
View at: Publisher Site | Google Scholar
Y. A. Chen and R. H. Scheller, “SNARE-mediated membrane fusion,” Nature Reviews Molecular Cell Biology, vol. 2, no. 2, pp. 98–106, 2001.
View at: Publisher Site | Google Scholar
J. Di Giovanni, C. C. Iborra, Y. Maulet, C. Lévêque, O. El Far, and M. Seagar, “Calcium-dependent regulation of SNARE-mediated membrane fusion by calmodulin,” Journal of Biological Chemistry, vol. 285, no. 31, pp. 23665–23675, 2010.
View at: Publisher Site | Google Scholar
R. Schneggenburger and E. Neher, “Intracellular calcium dependence of transmitter release rates at a fast central synapse,” Nature, vol. 406, no. 6798, pp. 889–993, 2000.
View at: Publisher Site | Google Scholar
X. S. Wu, B. D. McNeil, J. Xu et al., “Ca²⁺ and calmodulin initiate all forms of endocytosis during depolarization at a nerve terminal,” Nature Neuroscience, vol. 12, no. 8, pp. 1003–1010, 2009.
View at: Publisher Site | Google Scholar
A. Lee, S. T. Wong, D. Gallagher et al., “Ca²⁺/calmodulin binds to and modulates P/Q-type calcium channels,” Nature, vol. 399, no. 6732, pp. 155–159, 1999.
View at: Publisher Site | Google Scholar
M. Popoli, “Synaptotagmin is endogenously phosphorylated by Ca²⁺/calmodulin protein kinase II in synaptic vesicles,” FEBS Letters, vol. 317, no. 1–2, pp. 85–88, 1993.
View at: Publisher Site | Google Scholar
J. B. Park, C. C. Farnsworth, and J. A. Glomset, “Ca²⁺/calmodulin causes Rab3a to dissociate from synaptic membranes,” Journal of Biological Chemistry, vol. 272, no. 33, pp. 20857–20865, 1997.
View at: Publisher Site | Google Scholar
H. J. Junge, J. S. Rhee, O. Jahn et al., “Calmodulin and Munc13 form a Ca²⁺ sensor/effector complex that controls short-term synaptic plasticity,” Cell, vol. 118, no. 3, pp. 389–401, 2004.
View at: Publisher Site | Google Scholar
B. Marks and H. T. McMahon, “Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals,” Current Biology, vol. 8, no. 13, pp. 740–749, 1998.
View at: Google Scholar
M. Müller, F. Felmy, B. Schwaller, and R. Schneggenburger, “Parvalbumin is a mobile presynaptic Ca²⁺ buffer in the calyx of held that accelerates the decay of Ca²⁺ and short-term facilitation,” Journal of Neuroscience, vol. 27, no. 9, pp. 2261–2271, 2007.
View at: Publisher Site | Google Scholar
O. Caillard, H. Moreno, B. Schwaller, I. Llano, M. R. Celio, and A. Marty, “Role of the calcium-binding protein parvalbumin in short-term synaptic plasticity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 24, pp. 13372–13377, 2000.
View at: Publisher Site | Google Scholar
F. Felmy and R. Schneggenburger, “Developmental expression of the Ca²⁺-binding proteins calretinin and parvalbumin at the calyx of Held of rats and mice,” European Journal of Neuroscience, vol. 20, no. 6, pp. 1473–1482, 2004.
View at: Publisher Site | Google Scholar
S. Mochida, “Protein-protein interactions in neurotransmitter release,” Neuroscience Research, vol. 36, no. 3, pp. 175–182, 2000.
View at: Publisher Site | Google Scholar
T. C. Sudhof, “The synaptic vesicle cycle: a cascade of protein-protein interactions,” Nature, vol. 375, no. 6533, pp. 645–653, 1995.
View at: Google Scholar
S. Takamori, M. Holt, K. Stenius et al., “Molecular anatomy of a trafficking organelle,” Cell, vol. 127, no. 4, pp. 831–846, 2006.
View at: Publisher Site | Google Scholar
H. Ma and S. Mochida, “A cholinergic model synapse to elucidate protein function at presynatic terminals,” Neuroscience Research, vol. 57, no. 4, pp. 491–498, 2007.
View at: Publisher Site | Google Scholar
S. Mochida, Y. Nonomura, and H. Kobayashi, “Analysis of the mechanism for acetylcholine release at the synapse formed between rat sympathetic neurons in culture,” Microscopy Research and Technique, vol. 29, no. 2, pp. 94–102, 1994.
View at: Google Scholar
S. Mochida, H. Kobayashi, Y. Matsuda, Y. Yuda, K. Muramoto, and Y. Nonomura, “Myosin II is involved in transmitter release at synapses formed between rat sympathetic neurons in culture,” Neuron, vol. 13, no. 5, pp. 1131–1142, 1994.
View at: Publisher Site | Google Scholar
T. Baba, T. Sakisaka, S. Mochida, and Y. Takai, “PKA-catalyzed phosphorylation of tomosyn and its implication in Ca²⁺ -dependent exocytosis of neurotransmitter,” Journal of Cell Biology, vol. 170, no. 7, pp. 1113–1125, 2005.
View at: Publisher Site | Google Scholar
G. Krapivinsky, S. Mochida, L. Krapivinsky, S. M. Cibulsky, and D. Clapham, “The TRPM7 ion channel functions in cholinergic synaptic vesicles and affects transmitter release,” Neuron, vol. 52, no. 3, pp. 485–496, 2006.
View at: Publisher Site | Google Scholar
S. Mochida, A. P. Few, T. Scheuer, and W. A. Catterall, “Regulation of presynaptic C $a_{V}$ 2.1 Channels by Ca²⁺ sensor proteins mediates short-term synaptic plasticity,” Neuron, vol. 57, no. 2, pp. 210–216, 2008.
View at: Publisher Site | Google Scholar
S. Mochida, R. E. Westenbroek, C. T. Yokoyama, K. Itoh, and W. A. Catterall, “Subtype-selective reconstitution of synaptic transmission in sympathetic ganglion neurons by expression of exogenous calcium channels,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 5, pp. 2813–2818, 2003.
View at: Publisher Site | Google Scholar
Y. Nakajima, S. Mochida, K. Okawa, and S. Nakanishi, “Ca²⁺-dependent release of Munc18-1 from presynaptic mGluRs in short-term facilitation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 43, pp. 18385–18389, 2009.
View at: Publisher Site | Google Scholar
H. Ma, Q. Cai, W. Lu, Z. H. Sheng, and S. Mochida, “KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons,” Journal of Neuroscience, vol. 29, no. 41, pp. 13019–13029, 2009.
View at: Publisher Site | Google Scholar
R. E. Westenbroek, T. Sakurai, E. M. Elliott et al., “Immunochemical identification and subcellular distribution of the α(1A) subunits of brain calcium channels,” Journal of Neuroscience, vol. 15, no. 10, pp. 6403–6418, 1995.
View at: Google Scholar
K. Dunlap, J. I. Luebke, and T. Turner, “Exocytotic Ca²⁺ channels in mammalian central neurons,” Trends in Neurosciences, vol. 18, no. 2, pp. 89–98, 1995.
View at: Publisher Site | Google Scholar
R. M. Evans and G. W. Zamponi, “Presynaptic Ca²⁺ channels—integration centers for neuronal signaling pathways,” Trends in Neurosciences, vol. 29, no. 11, pp. 617–624, 2006.
View at: Publisher Site | Google Scholar
W. A. Catterall, “Structure and regulation of voltage-gated Ca²⁺ channels,” Annual Review of Cell and Developmental Biology, vol. 16, pp. 521–555, 2000.
View at: Publisher Site | Google Scholar
C. D. DeMaria, T. W. Soong, B. A. Alseikhan, R. S. Alvania, and D. T. Yue, “Calmodulin bifurcates the local Ca²⁺ signal that modulates P/Q-type Ca²⁺ channels,” Nature, vol. 411, no. 6836, pp. 484–489, 2001.
View at: Publisher Site | Google Scholar
A. Lee, T. Scheuer, and W. A. Catterall, “Ca²⁺/calmodulin-dependent facilitation and inactivation of P/Q-type Ca²⁺ channels,” Journal of Neuroscience, vol. 20, no. 18, pp. 6830–6838, 2000.
View at: Google Scholar
A. Lee, H. Zhou, T. Scheuer, and W. A. Catterall, “Molecular determinants of Ca²⁺/calmodulin-dependent regulation of C $a_{V}$ 2.1 channels,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 26, pp. 16059–16064, 2003.
View at: Publisher Site | Google Scholar
A. P. Few, N. J. Lautermilch, R. E. Westenbroek, T. Scheuer, and W. A. Catterall, “Differential regulation of C $a_{V}$ 2.1 channels by calcium-binding protein 1 and visinin-like protein-2 requires N-terminal myristoylation,” Journal of Neuroscience, vol. 25, no. 30, pp. 7071–7080, 2005.
View at: Publisher Site | Google Scholar
N. J. Lautermilch, A. P. Few, T. Scheuer, and W. A. Catterall, “Modulation of C $a_{V}$ 2.1 channels by the neuronal calcium-binding protein visinin-like protein-2,” Journal of Neuroscience, vol. 25, no. 30, pp. 7062–7070, 2005.
View at: Publisher Site | Google Scholar
A. Lee, R. E. Westenbroek, F. Haeseleer, K. Palczewski, T. Scheuer, and W. A. Catterall, “Differential modulation of C $a_{V}$ 2.1 channels by calmodulin and Ca²⁺-binding protein 1,” Nature Neuroscience, vol. 5, no. 3, pp. 210–217, 2002.
View at: Publisher Site | Google Scholar
I. D. Forsythe, T. Tsujimoto, M. Barnes-Davies, M. F. Cuttle, and T. Takahashi, “Inactivation of presynaptic calcium current contributes to synaptic depression at a fast central synapse,” Neuron, vol. 20, no. 4, pp. 797–807, 1998.
View at: Publisher Site | Google Scholar
J. Xu and L. G. Wu, “The decrease in the presynaptic calcium current is a major cause of short-term depression at a calyx-type synapse,” Neuron, vol. 46, no. 4, pp. 633–645, 2005.
View at: Publisher Site | Google Scholar
D. Chaudhuri, B. A. Alseikhan, S. Y. Chang, T. W. Soong, and D. T. Yue, “Developmental activation of calmodulin-dependent facilitation of cerebellar P-type Ca²⁺ current,” Journal of Neuroscience, vol. 25, no. 36, pp. 8282–8294, 2005.
View at: Publisher Site | Google Scholar
J. G. G. Borst and B. Sakmann, “Facilitation of presynaptic calcium currents in the rat brainstem,” Journal of Physiology, vol. 513, no. 1, pp. 149–155, 1998.
View at: Google Scholar
R. S. Zucker and W. G. Regehr, “Short-term synaptic plasticity,” Annual Review of Physiology, vol. 64, pp. 355–405, 2002.
View at: Publisher Site | Google Scholar
C. F. Stevens and J. F. Wesseling, “Augmentation is a potentiation of the exocytotic process,” Neuron, vol. 22, no. 1, pp. 139–146, 1999.
View at: Publisher Site | Google Scholar
K. L. Magleby, “The effect of tetanic and post tetanic potentiation on facilitation of transmitter release at the frog neuromuscular junction,” Journal of Physiology, vol. 234, no. 2, pp. 353–371, 1973.
View at: Google Scholar
K. L. Magleby and J. E. Zengel, “A dual effect of repetitive stimulation on post tetanic potentiation of transmitter release at the frog neuromuscular junction,” Journal of Physiology, vol. 245, no. 1, pp. 163–182, 1975.
View at: Google Scholar
Y. G. Tang and R. S. Zucker, “Mitochondrial involvement in post-tetanic potentiation of synaptic transmission,” Neuron, vol. 18, no. 3, pp. 483–491, 1997.
View at: Publisher Site | Google Scholar
M. Beierlein, D. Fioravante, and W. G. Regehr, “Differential expression of posttetanic potentiation and retrograde signaling mediate target-dependent short-term synaptic plasticity,” Neuron, vol. 54, no. 6, pp. 949–959, 2007.
View at: Publisher Site | Google Scholar
D. H. Brager, X. Cai, and S. M. Thompson, “Activity-dependent activation of presynaptic protein kinase C mediates post-tetanic potentiation,” Nature Neuroscience, vol. 6, no. 6, pp. 551–552, 2003.
View at: Publisher Site | Google Scholar
L. F. Abbott and W. G. Regehr, “Synaptic computation,” Nature, vol. 431, no. 7010, pp. 796–803, 2004.
View at: Publisher Site | Google Scholar
M. Lorez, U. Humbel, M. C. Pflimlin, and J. N. C. Kew, “Group III metabotropic glutamate receptors as autoreceptors in the cerebellar cortex,” British Journal of Pharmacology, vol. 138, no. 4, pp. 614–625, 2003.
View at: Publisher Site | Google Scholar
S. Nakanishi, “Molecular diversity of glutamate receptors and implications for brain function,” Science, vol. 258, no. 5082, pp. 597–603, 1992.
View at: Google Scholar
J. P. Pin and R. Duvoisin, “The metabotropic glutamate receptors: structure and functions,” Neuropharmacology, vol. 34, no. 1, pp. 1–26, 1995.
View at: Publisher Site | Google Scholar
R. Shigemoto, A. Kinoshita, E. Wada et al., “Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus,” Journal of Neuroscience, vol. 17, no. 19, pp. 7503–7522, 1997.
View at: Google Scholar
R. Pekhletski, R. Gerlai, L. S. Overstreet et al., “Impaired cerebellar synaptic plasticity and motor performance in mice lacking the mGluR4 subtype of metabotropic glutamate receptor,” Journal of Neuroscience, vol. 16, no. 20, pp. 6364–6373, 1996.
View at: Google Scholar
V. O'Connor, O. El Far, E. Bofill-Cardona et al., “Calmodulin dependence of presynaptic metabotropic glutamate receptor signaling,” Science, vol. 286, no. 5442, pp. 1180–1184, 1999.
View at: Publisher Site | Google Scholar
D. Chin and A. R. Means, “Calmodulin: a prototypical calcium sensor,” Trends in Cell Biology, vol. 10, no. 8, pp. 322–328, 2000.
View at: Publisher Site | Google Scholar
J. Rizo and T. C. Südhof, “Snares and munc18 in synaptic vesicle fusion,” Nature Reviews Neuroscience, vol. 3, no. 8, pp. 641–653, 2002.
View at: Google Scholar
J. Shen, D. C. Tareste, F. Paumet, J. E. Rothman, and T. J. Melia, “Selective activation of cognate SNAREpins by Sec1/Munc18 proteins,” Cell, vol. 128, no. 1, pp. 183–195, 2007.
View at: Publisher Site | Google Scholar
K. M. S. Misura, R. H. Scheller, and W. I. Weis, “Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex,” Nature, vol. 404, no. 6776, pp. 355–362, 2000.
View at: Publisher Site | Google Scholar
Y. Nakajima, T. Yamamoto, T. Nakayama, and S. Nakanishi, “A relationship between protein kinase C phosphorylation and calmodulin binding to the metabotropic glutamate receptor subtype 7,” Journal of Biological Chemistry, vol. 274, no. 39, pp. 27573–27577, 1999.
View at: Publisher Site | Google Scholar
P. J. Kammermeier and S. R. Ikedal, “Metabotropic glutamate receptor expression in the rat superior cervical ganglion,” Neuroscience Letters, vol. 330, no. 3, pp. 260–264, 2002.
View at: Publisher Site | Google Scholar
H. L. Atwood and S. Karunanithi, “Diversification of synaptic strength: presynaptic elements,” Nature Reviews Neuroscience, vol. 3, no. 7, pp. 497–516, 2002.
View at: Publisher Site | Google Scholar
J. S. Dittman, A. C. Kreitzer, and W. G. Regehr, “Interplay between facilitation, depression, and residual calcium at three presynaptic terminals,” Journal of Neuroscience, vol. 20, no. 4, pp. 1374–1385, 2000.
View at: Google Scholar
S. Mochida, Z. -H. Sheng, C. Baker, H. Kobayashi, and W. A. Catterall, “Inhibition of neurotransmission by peptides containing the synaptic protein interaction site of N-type Ca2+ channels,” Neuron, vol. 17, no. 4, pp. 781–788, 1996.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2011 Sumiko Mochida. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

1398

Downloads

1082

Citations