GABAA-receptor-associated protein links GABAA receptors and the cytoskeleton

被引:484
作者
Wang, HB
Bedford, FK
Brandon, NJ
Moss, SJ
Olsen, RW [1 ]
机构
[1] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA
[2] UCL, MRC, Lab Mol & Cell Biol, London WC1E 6BT, England
[3] UCL, Dept Pharmacol, London WC1E 6BT, England
[4] Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
关键词
D O I
10.1038/16264
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Type-A receptors for the neurotransmitter GABA (gamma-aminobutyric acid) are ligand-gated chloride channels that mediate inhibitory neurotransmission. Each subunit of the pentameric receptor protein has ligand-binding sites in the amino-terminal extracellular domain and four membrane-spanning regions, one of which forms a wall of the ion channel(1). Each subunit also has a large intracellular loop that may be a target for protein kinases and be required for subcellular targeting and membrane clustering of the receptor, perhaps by anchoring the receptor to the cytoskeleton(2-4) Neurotransmitter receptors need to be positioned in high density in the cell membrane at sites postsynaptic to nerve terminals releasing that neurotransmitter, Other members of the superfamily of ligand-gated ion-channel receptors associate in postsynaptic-membrane clusters by binding to the proteins rapsyn or gephyrin(5-7). Here we identify a new cellular protein, GABA(A)-receptor-associated protein (GABARAP), which can interact with the gamma 2 subunit of GABA(A) receptors, GABARAP binds to GABA(A) receptors both in vitro and in vivo, and co-localizes with the punctate staining of GABA(A) receptors on cultured cortical neurons, Sequence analysis shows similarity between GABARAP and light chain-3 of microtubule-associated proteins 1A and 1B. Moreover, the N terminus of GABARAP is highly positively charged and features a putative tubulin-binding motif. The interactions among GABA(A) receptors, GABARAP and tubulin suggest a mechanism for the targeting and clustering of GABA(A) receptors.
引用
收藏
页码:69 / 72
页数:4
相关论文
共 21 条