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(Received for publication, June 2, 1997, and in revised form, June 24, 1997)
From the
Volume 272, Number 34,
Issue of August 22, 1997
pp. 21504-21508
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
-Latrotoxin Receptor, Latrophilin, Is a Novel Member of the
Secretin Family of G Protein-coupled Receptors
,
,
,
Department of Biochemistry,
-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 G
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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