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

J Biol Chem. 1997 Aug 22;272(34):21504-8. doi: 10.1074/jbc.272.34.21504.

Abstract

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 Galphao 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Exocytosis
  • GTP-Binding Proteins / physiology
  • Membrane Glycoproteins / chemistry
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Rats
  • Receptors, Peptide / chemistry
  • Receptors, Peptide / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Spider Venoms / metabolism*
  • Synaptic Vesicles / metabolism

Substances

  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Receptors, Peptide
  • Spider Venoms
  • alpha-latrotoxin receptor
  • alpha-latrotoxin
  • GTP-Binding Proteins

Associated data

  • GENBANK/AF081146
  • GENBANK/U78105