PMID- 10026162
OWN - NLM
STAT- MEDLINE
DCOM- 19990318
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 9
DP  - 1999 Feb 26
TI  - A novel ubiquitously expressed alpha-latrotoxin receptor is a member of the CIRL 
      family of G-protein-coupled receptors.
PG  - 5491-8
AB  - Poisoning with alpha-latrotoxin, a neurotoxic protein from black widow spider
      venom, results in a robust increase of spontaneous synaptic transmission and
      subsequent degeneration of affected nerve terminals. The neurotoxic action of
      alpha-latrotoxin involves extracellular binding to its high affinity receptors as
      a first step. One of these proteins, CIRL, is a neuronal G-protein-coupled
      receptor implicated in the regulation of secretion. We now demonstrate that CIRL 
      has two close homologs with a similar domain structure and high degree of overall
      identity. These novel receptors, which we propose to name CIRL-2 and CIRL-3,
      together with CIRL (CIRL-1) belong to a recently identified subfamily of large
      orphan receptors with structural features typical of both G-protein-coupled
      receptors and cell adhesion proteins. Northern blotting experiments indicate that
      CIRL-2 is expressed ubiquitously with highest concentrations found in placenta,
      kidney, spleen, ovary, heart, and lung, whereas CIRL-3 is expressed predominantly
      in brain similarly to CIRL-1. It appears that CIRL-2 can also bind
      alpha-latrotoxin, although its affinity to the toxin is about 14 times less than 
      that of CIRL-1. When overexpressed in chromaffin cells, CIRL-2 increases their
      sensitivity to alpha-latrotoxin stimulation but also inhibits Ca2+-regulated
      secretion. Thus, CIRL-2 is a functionally competent receptor of alpha-latrotoxin.
      Our findings suggest that although the nervous system is the primary target of
      low doses of alpha-latrotoxin, cells of other tissues are also susceptible to the
      toxic effects of alpha-latrotoxin because of the presence of CIRL-2, a low
      affinity receptor of the toxin.
FAU - Ichtchenko, K
AU  - Ichtchenko K
AD  - Departments of Pharmacology, New York University Medical Center, New York, 10016,
      USA. ichtck01@mcrcr.med.nyu.edu
FAU - Bittner, M A
AU  - Bittner MA
FAU - Krasnoperov, V
AU  - Krasnoperov V
FAU - Little, A R
AU  - Little AR
FAU - Chepurny, O
AU  - Chepurny O
FAU - Holz, R W
AU  - Holz RW
FAU - Petrenko, A G
AU  - Petrenko AG
LA  - eng
SI  - GENBANK/AF063102
SI  - GENBANK/AF063103
GR  - R01DK27959/DK/NIDDK NIH HHS/United States
GR  - R01NS34937/NS/NINDS NIH HHS/United States
GR  - R01NS35098/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Receptors, Peptide)
RN  - 0 (alpha-latrotoxin receptor)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Chromaffin Cells/metabolism
MH  - Cloning, Molecular
MH  - DNA Primers
MH  - DNA, Complementary
MH  - GTP-Binding Proteins/*metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Protein Binding
MH  - Rats
MH  - Receptors, Peptide/chemistry/genetics/*metabolism
MH  - Sequence Homology, Amino Acid
EDAT- 1999/02/20 00:00
MHDA- 1999/02/20 00:01
CRDT- 1999/02/20 00:00
PHST- 1999/02/20 00:00 [pubmed]
PHST- 1999/02/20 00:01 [medline]
PHST- 1999/02/20 00:00 [entrez]
AID - 10.1074/jbc.274.9.5491 [doi]
AID - S0021-9258(19)87685-8 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Feb 26;274(9):5491-8. doi: 10.1074/jbc.274.9.5491.