Trans-Synaptic Regulation of Dendritic Spine Morphology

Science's STKE  04 Feb 2003:
Vol. 2003, Issue 168, pp. tw53-TW53
DOI: 10.1126/stke.2003.168.tw53

Penzes et al. investigated the role of the EphB2 receptor, which has been implicated in synaptic plasticity and dendritic spine formation, and discovered a transynaptic pathway linking ephrinB to spine morphogenesis through the guanine nucleotide exchange factor (GEF) kalirin. Dendritic spines, small protrusions that permit compartmentalization of input from excitatory synapses, show dynamic changes during development and in adulthood. In adults, changes in spine number, size, and shape have been associated with synaptic plasticity, learning, and aging. Kalirin can modulate Rac-1 regulation of the actin cytoskeleton and thus changes in spine morphology. The signals regulating kalirin activity, however, have remained unclear. Penzes et al. visualized cultured hippocampal neurons and showed that clustered ephrinB1 triggered the formation of spines, which made contacts with presynaptic terminals. The authors used Western analysis on kalirin immunoprecipitates in combination with immunocytochemical analysis to show that ephrinB1 stimulated kalirin phosphorylation and recruitment of kalirin clusters to synapses. The effects of ephrinB1 on spine morphology and kalirin clustering were inhibited by a dominant-negative mutant EphB2, which lacks kinase activity. Similarly, a GEF-inactive kalirin-7 mutant and a dominant-negative Rac-1 mutant both inhibited the effects of ephrinB1 on spine morphology. EphrinB1 treatment lead to activation (autophosphorylation) of the Rac-1 effector p21-activated kinase (PAK) and to clustering of phosphorylated PAK at synapses. Inhibiting PAK eliminated the effects of ephrinB1 on spine morphogenesis. These data suggest that clustering of presynaptic ephrinB leads to clustering and activation of postsynaptic EphB, kalirin recruitment, and rearrangement of the cytoskeleton mediated by Rac-1 and PAK.

P. Penzes, A. Beeser, J. Chernoff, M. R. Schiller, B. A. Eipper, R. E. Mains, R. L. Huganir, Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin. Neuron 37, 263-274 (2003). [Online Journal]