%0 Journal Article
%T Thrombospondin receptor ¦Á2¦Ä-1 promotes synaptogenesis and spinogenesis via postsynaptic Rac1
%A Cagla
%A Cagla Eroglu
%A Choi
%A Debra L.
%A Debra L. Silver
%A Dongqing
%A Dongqing Wang
%A Erin F.
%A Erin F. Spence
%A Eroglu
%A Feng
%A Guoping
%A Guoping Feng
%A Henry H.
%A Henry H. Yin
%A Ji-Eun
%A Ji-Eun Choi
%A Kim
%A Koh
%A Louis-Jan
%A Louis-Jan Pilaz
%A Mitev
%A Namsoo
%A Namsoo Kim
%A Petar
%A Petar Mitev
%A Pilaz
%A Risher
%A Scott H.
%A Scott H. Soderling
%A Sehwon
%A Sehwon Koh
%A Silver
%A Soderling
%A Spence
%A W. Christopher
%A W. Christopher Risher
%A Wang
%A Yin
%J JCB | The Journal of Cell Biology
%D 2018
%R 10.1083/jcb.201802057
%X Astrocytes control excitatory synaptogenesis by secreting thrombospondins (TSPs), which function via their neuronal receptor, the calcium channel subunit ¦Á2¦Ä-1. ¦Á2¦Ä-1 is a drug target for epilepsy and neuropathic pain; thus the TSP¨C¦Á2¦Ä-1 interaction is implicated in both synaptic development and disease pathogenesis. However, the mechanism by which this interaction promotes synaptogenesis and the requirement for ¦Á2¦Ä-1 for connectivity of the developing mammalian brain are unknown. In this study, we show that global or cell-specific loss of ¦Á2¦Ä-1 yields profound deficits in excitatory synapse numbers, ultrastructure, and activity and severely stunts spinogenesis in the mouse cortex. Postsynaptic but not presynaptic ¦Á2¦Ä-1 is required and sufficient for TSP-induced synaptogenesis in vitro and spine formation in vivo, but an ¦Á2¦Ä-1 mutant linked to autism cannot rescue these synaptogenesis defects. Finally, we reveal that TSP¨C¦Á2¦Ä-1 interactions control synaptogenesis postsynaptically via Rac1, suggesting potential molecular mechanisms that underlie both synaptic development and pathology.
%U http://jcb.rupress.org/content/217/10/3747