Kalirin-7 is a Key Player in the Formation of Excitatory Synapses in Hippocampal Neurons

Xin-Ming Ma

doi:10.1100/tsw.2010.148

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 (Kal7) 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.

Highlights

The majority of excitatory glutamatergic synapses are localized on dendritic spines, which are small protrusions from the dendritic arbor in the brain[1]
Rho GTPases, which are activated by Rho guanine nucleotide exchange factors (GEFs) and inactivated by Rho GTPase activating proteins (GAPs), are important intracellular signaling switches in the regulation of cytoskeletal organization[23,24,25,26]
Kal7 is distinguished from other Kalirin isoforms by its unique 20-amino-acid C-terminal PDZ binding motif, which allows Kal7 to interact with several PDZ domain–containing proteins[41] (Fig. 1)

Summary

Introduction

The majority of excitatory glutamatergic synapses are localized on dendritic spines, which are small protrusions from the dendritic arbor in the brain[1]. Reduced expression of the most major Kalirin isoforms (Kal7, 9, and 12) causes simplification of the dendritic tree and a marked decrease of spine density, with dispersion of postsynaptic density markers and elimination of presynaptic endings in hippocampal CA1 pyramidal neurons[39]. These data suggest that Kal7 might play an important role in the regulation of excitatory synapse formation.

Results

Conclusion