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Volume 272, Number 34, Issue of August 22, 1997 pp. 21504-21508
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

alpha -Latrotoxin Receptor, Latrophilin, Is a Novel Member of the Secretin Family of G Protein-coupled Receptors

(Received for publication, June 2, 1997, and in revised form, June 24, 1997)

Vera G. Lelianova Dagger , Bazbek A. Davletov Dagger , Alistair Sterling § , M. Atiqur Rahman Dagger , Eugene V. Grishin , Nicholas F. Totty § and Yuri A. Ushkaryov Dagger

From the Dagger  Department of Biochemistry, Imperial College, Exhibition Road, London SW7 2AY and the § Ludwig Institute for Cancer Research, London W1P 8BT, United Kingdom and the  Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117871, Russia

alpha -Latrotoxin (LTX) stimulates massive exocytosis of synaptic vesicles and may 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 Galpha 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.


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