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Gene Review

Lphn1  -  latrophilin 1

Rattus norvegicus

Synonyms: CIRL-1, Calcium-independent alpha-latrotoxin receptor 1, Cirl, Cirl1, Cl1, ...
 
 
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Disease relevance of Lphn1

  • Furthermore, antisense oligonucleotides complementary to CIRL-1 mRNA or CIRL-3 mRNA suppressed neuronal death associated with hypoxia in hippocampal and cortical cell cultures [1].
 

High impact information on Lphn1

  • Expression of CIRL in chromaffin cells increases the sensitivity of the cells to the effects of alpha-latrotoxin, demonstrating that this protein is functional in coupling to secretion [2].
  • CIRL appears to be a novel orphan G-protein-coupled receptor, a member of the secretin receptor family [2].
  • Interaction of CIRL with a specific presynaptic neurotoxin and with a component of the docking-fusion machinery suggests its role in regulation of neurosecretion [2].
  • Vesicle exocytosis stimulated by alpha-latrotoxin is mediated by latrophilin and requires both external and stored Ca2+ [3].
  • These data, together with binding studies, prove that latrophilin, which is linked to G proteins and inositol polyphosphate production, is the major functional LTX receptor [3].
 

Biological context of Lphn1

 

Anatomical context of Lphn1

  • Upon expression in COS cells, the cloned protein is indistinguishable from brain latrophilin and binds LTX with high affinity [7].
  • This presumably membrane-bound protein is localized to and differentially distributed among neuronal tissues, with about four times more latrophilin expressed in the cerebral cortex than in the cerebellum; subcellular fractionation showed that the protein is highly enriched in synaptosomal plasma membranes [8].
  • This protein, termed here latrophilin, has been purified from detergent-solubilized bovine brain membranes by affinity chromatography on immobilized alpha-latrotoxin and concentrated on a wheat germ agglutinin affinity column [8].
  • 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 [7].
  • In contrast with canonic GPCRs, CIRL consists of two heterologous non-covalently bound subunits, p120 and p85, due to endogenous proteolytic processing of the receptor precursor in the endoplasmic reticulum [6].
 

Associations of Lphn1 with chemical compounds

  • Sucrose gradient centrifugations demonstrated that latrophilin and alpha-latrotoxin form a stable equimolar complex [8].
  • We determined that the site of the CIRL cleavage is located within a juxtamembrane Cys- and Trp-rich domain of the N-terminal extracellular region of CIRL [6].
  • By day 21, staining was identical to that of adult animals, but as this is an age when androgen levels are not at their peak, the data would suggest that they are not a prominent factor regulating Cl-1 expression [9].
  • However, in all other epididymal regions, orchidectomy with or without testosterone replacement, revealed no changes to the normal staining pattern, suggesting that androgens do not regulate Cl-1 expression in these regions [9].
  • Norepinephrine exocytosis stimulated by alpha-latrotoxin requires both external and stored Ca2+ and is mediated by latrophilin, G proteins and phospholipase C [10].
 

Physical interactions of Lphn1

  • To test this hypothesis, we used conditions (substitution of Ca2+ in the medium with Sr2+) under which LTXN4C does not bind to any member of the neurexin family but still interacts with latrophilin [11].
 

Other interactions of Lphn1

 

Analytical, diagnostic and therapeutic context of Lphn1

  • We describe molecular cloning and functional expression of the calcium-independent receptor of alpha-latrotoxin (CIRL), which is a second high affinity alpha-latrotoxin receptor that may be the major mediator of alpha-latrotoxin's effects [2].
  • Northern blot analysis shows that latrophilin message is present only in neuronal tissue [7].
  • Latrophilin physically interacts with a Galphao subunit of heterotrimeric G proteins, because the two proteins co-purify in a two-step affinity chromatography [7].
  • RT-PCR of adult epididymal and testicular RNA (positive control) indicated that Cl-1 messenger RNA (mRNA) transcripts were present in all regions of the epididymis [9].
  • In the present study the expression of claudin-l (Cl-1) was examined with respect to the different cell types of the epididymis and its various regions as well as its expression during postnatal development and regulation by testicular factors, using both immunocytochemistry and Northern blot analysis [9].

References

  1. Involvement of the calcium-independent receptor for alpha-latrotoxin in brain ischemia. Bin Sun, H., Ruan, Y., Xu, Z.C., Yokota, H. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  2. alpha-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Krasnoperov, V.G., Bittner, M.A., Beavis, R., Kuang, Y., Salnikow, K.V., Chepurny, O.G., Little, A.R., Plotnikov, A.N., Wu, D., Holz, R.W., Petrenko, A.G. Neuron (1997) [Pubmed]
  3. Vesicle exocytosis stimulated by alpha-latrotoxin is mediated by latrophilin and requires both external and stored Ca2+. Davletov, B.A., Meunier, F.A., Ashton, A.C., Matsushita, H., Hirst, W.D., Lelianova, V.G., Wilkin, G.P., Dolly, J.O., Ushkaryov, Y.A. EMBO J. (1998) [Pubmed]
  4. The latrophilin family: multiply spliced G protein-coupled receptors with differential tissue distribution. Matsushita, H., Lelianova, V.G., Ushkaryov, Y.A. FEBS Lett. (1999) [Pubmed]
  5. Structural requirements for alpha-latrotoxin binding and alpha-latrotoxin-stimulated secretion. A study with calcium-independent receptor of alpha-latrotoxin (CIRL) deletion mutants. Krasnoperov, V., Bittner, M.A., Holz, R.W., Chepurny, O., Petrenko, A.G. J. Biol. Chem. (1999) [Pubmed]
  6. Post-translational proteolytic processing of the calcium-independent receptor of alpha-latrotoxin (CIRL), a natural chimera of the cell adhesion protein and the G protein-coupled receptor. Role of the G protein-coupled receptor proteolysis site (GPS) motif. Krasnoperov, V., Lu, Y., Buryanovsky, L., Neubert, T.A., Ichtchenko, K., Petrenko, A.G. J. Biol. Chem. (2002) [Pubmed]
  7. Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. Lelianova, V.G., Davletov, B.A., Sterling, A., Rahman, M.A., Grishin, E.V., Totty, N.F., Ushkaryov, Y.A. J. Biol. Chem. (1997) [Pubmed]
  8. Isolation and biochemical characterization of a Ca2+-independent alpha-latrotoxin-binding protein. Davletov, B.A., Shamotienko, O.G., Lelianova, V.G., Grishin, E.V., Ushkaryov, Y.A. J. Biol. Chem. (1996) [Pubmed]
  9. Claudin-1 is not restricted to tight junctions in the rat epididymis. Gregory, M., Dufresne, J., Hermo, L., Cyr, D. Endocrinology (2001) [Pubmed]
  10. Norepinephrine exocytosis stimulated by alpha-latrotoxin requires both external and stored Ca2+ and is mediated by latrophilin, G proteins and phospholipase C. Rahman, M.A., Ashton, A.C., Meunier, F.A., Davletov, B.A., Dolly, J.O., Ushkaryov, Y.A. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1999) [Pubmed]
  11. Mutant alpha-latrotoxin (LTXN4C) does not form pores and causes secretion by receptor stimulation: this action does not require neurexins. Volynski, K.E., Capogna, M., Ashton, A.C., Thomson, D., Orlova, E.V., Manser, C.F., Ribchester, R.R., Ushkaryov, Y.A. J. Biol. Chem. (2003) [Pubmed]
  12. A novel ubiquitously expressed alpha-latrotoxin receptor is a member of the CIRL family of G-protein-coupled receptors. Ichtchenko, K., Bittner, M.A., Krasnoperov, V., Little, A.R., Chepurny, O., Holz, R.W., Petrenko, A.G. J. Biol. Chem. (1999) [Pubmed]
  13. Olfactory receptors, Golf alpha and adenylyl cyclase mRNA expressions in the rat heart during ontogenic development. Ferrand, N., Pessah, M., Frayon, S., Marais, J., Garel, J.M. J. Mol. Cell. Cardiol. (1999) [Pubmed]
 
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