Regulation of the Postsynaptic Compartment of Excitatory Synapses by the Actin Cytoskeleton in Health and Its Disruption in Disease

Figure 1

Schematic representation of the cytoskeleton-dependent trafficking of neurotransmitter receptors. Depicted are the key structures of the synapse and associated cytoskeletal molecules. Numbers indicate the following steps: (1) Myosin V traffics vesicles with receptors from the soma to the distal dendritic sites via microtubules (MT) [116]. MT plus ends are indicated by green circles. (2) Once within spines, myosin V transports receptors to plasma membrane via actin filaments [117]. (3) Anchoring of receptors in the PSD relies on myosin II contractile force on actin cytoskeleton in combination with constant actin treadmilling/turnover [48]. Lateral diffusion of receptors to and from the PSD to presynaptic regions can occur. (4) Receptor internalization involves myosin VI activity. Myosin VI transports internalized receptors to endosomal organelles, facilitating recycling of receptors back to the membrane or to degradation pathways [95]. (5) Receptors can also travel between the PSD and peripheral sites [118, 119].