RGD Reference Report - Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. - Rat Genome Database

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

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 
Citation: Eroglu C, etal., Cell. 2009 Oct 16;139(2):380-92. doi: 10.1016/j.cell.2009.09.025. Epub 2009 Oct 8.
RGD ID: 8553976
Pubmed: PMID:19818485   (View Abstract at PubMed)
PMCID: PMC2791798   (View Article at PubMed Central)
DOI: DOI:10.1016/j.cell.2009.09.025   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:P354428553976PMID:19818485IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Cacna2d1  (calcium voltage-gated channel auxiliary subunit alpha2delta 1)


Additional Information