alpha-Latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors

alpha-Latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors
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DOI:
10.1074/jbc.272.34.21504
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发表时间:
1997-08-22
影响因子:
4.8
通讯作者:
Ushkaryov, YA
Ushkaryov, YA
中科院分区:
生物学2区
文献类型:
--
作者:
Lelianova, VG;Davletov, BA;Ushkaryov, YA

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α-latrotoxin(LTX)刺激突触囊泡的大量胞吐作用,有助于阐明神经分泌的调节机制。现在我们证明了latrophilin是参与分泌的G蛋白偶联受体的分泌素家族的新成员,北方印迹分析显示latrophilin信息仅存在于神经组织中,在COS细胞中表达后,克隆的蛋白与脑latrophilin无法区分,并且以高亲和力结合LTX,Latrophilin与异源三聚体G蛋白的G α(o)亚基物理相互作用,由于这两种蛋白质在两步亲和层析中共纯化,有趣的是,latrophilin的胞外结构域与嗅觉调节蛋白(olfactomedin)是同源的,嗅觉调节蛋白是一种被认为参与气味结合的可溶性神经元蛋白。我们的研究结果表明latrophilin可能结合未鉴定的内源性配体和神经末梢信号,从而暗示G蛋白参与突触囊泡胞吐的控制。
alpha-Latrotoxin (LTX) stimulates massive exocytosis of synaptic vesicles and mag help to elucidate the mechanism of regulation of neurosecretion, We have recently isolated latrophilin, the synaptic Ca2+-independent LTX receptor. Now we demonstrate that latrophilin is a novel member of the secretin family of G protein-coupled receptors that are involved in secretion, Northern blot analysis shows that latrophilin message is present only in neuronal tissue, Upon expression in COS cells, the cloned protein is indistinguishable from brain latrophilin and binds LTX with high affinity, Latrophilin physically interacts with a G alpha(o) subunit of heterotrimeric G proteins, because the two proteins co-purify in a two-step affinity chromatography, interestingly, extracellular domain of latrophilin is homologous to olfactomedin, a soluble neuronal protein thought to participate in odorant binding, Our findings suggest that latrophilin may bind unidentified endogenous ligands and transduce signals into nerve terminals, thus implicating G proteins in the control of synaptic vesicle exocytosis.