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TheScientificWorldJOURNAL
Volume 10 (2010), Pages 1655-1666
doi:10.1100/tsw.2010.148
Kalirin-7 is a Key Player in the Formation of Excitatory Synapses in Hippocampal Neurons
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT, USA
Received 14 May 2010; Revised 26 June 2010; Accepted 28 June 2010
Academic Editor: Sergi Ferre
Copyright © 2010 Xin-Ming Ma.
Abstract
Kalirin-7 (Kal7), a major isoform of Kalirin in the adult rodent hippocampus, is exclusively localized to the postsynaptic side of mature excitatory synapses in hippocampal neurons. Kal7 interacts with multiple PDZ domain—containing proteins through its unique PDZ binding motif. Overexpression of Kal7 increases spine density and spine size, whereas reduction of endogenous Kal7 expression by small hairpin RNA (shRNA) causes a decrease in synapse number and spine density in cultured hippocampal neurons. Hippocampal CA1 pyramidal neurons of Kal7 knockout (Kal7KO) mice show decreased spine density, spine length, synapse number, and postsynaptic density (PSD) size in their apical dendrites; are deficient in long-term potentiation (LTP); and exhibit decreased frequency of spontaneous excitatory postsynaptic current (sEPSC). Kal7 plays a key role in estrogen-mediated spine/synapse formation in hippocampal neurons. Kal7 is also an essential determinant of dendritic spine formation following chronic cocaine treatment. Kal7 plays a key role in excitatory synapse formation and function.