Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis.

Published

Journal Article

Synapses are asymmetric cellular adhesions that are critical for nervous system development and function, but the mechanisms that induce their formation are not well understood. We have previously identified thrombospondin as an astrocyte-secreted protein that promotes central nervous system (CNS) synaptogenesis. Here, we identify the neuronal thrombospondin receptor involved in CNS synapse formation as alpha2delta-1, the receptor for the anti-epileptic and analgesic drug gabapentin. We show that the VWF-A domain of alpha2delta-1 interacts with the epidermal growth factor-like repeats common to all thrombospondins. alpha2delta-1 overexpression increases synaptogenesis in vitro and in vivo and is required postsynaptically for thrombospondin- and astrocyte-induced synapse formation in vitro. Gabapentin antagonizes thrombospondin binding to alpha2delta-1 and powerfully inhibits excitatory synapse formation in vitro and in vivo. These findings identify alpha2delta-1 as a receptor involved in excitatory synapse formation and suggest that gabapentin may function therapeutically by blocking new synapse formation.

Full Text

Duke Authors

Cited Authors

  • Eroglu, C; Allen, NJ; Susman, MW; O'Rourke, NA; Park, CY; Ozkan, E; Chakraborty, C; Mulinyawe, SB; Annis, DS; Huberman, AD; Green, EM; Lawler, J; Dolmetsch, R; Garcia, KC; Smith, SJ; Luo, ZD; Rosenthal, A; Mosher, DF; Barres, BA

Published Date

  • October 16, 2009

Published In

Volume / Issue

  • 139 / 2

Start / End Page

  • 380 - 392

PubMed ID

  • 19818485

Pubmed Central ID

  • 19818485

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2009.09.025

Language

  • eng

Conference Location

  • United States