Alpha-latrotoxin and its receptors CIRL (latrophilin) and neurexin 1 alpha mediate effects on secretion through multiple mechanisms.
Alpha-Latrotoxin and its plasma membrane receptors cause a number of distinct effects in secretory cells. First, by tethering alpha-latrotoxin to the plasma membrane, CIRL/latrophilin and neurexin 1 alpha facilitate alpha-latrotoxin-induced channel formation. The stimulation of secretion by alpha-latrotoxin in neuroendocrine cells is a consequence of Ca(2+) influx through these alpha-latrotoxin-induced channels. In addition to channel formation, alpha-latrotoxin enhances secretion in permeabilized cells through interaction with the plasma membrane receptor CIRL/latrophilin. Finally, overexpression of CIRL/latrophilin inhibits Ca(2+)-dependent secretion in permeabilized chromaffin cells in the absence of alpha-latrotoxin. This effect represents a 'constitutive' action of the G-protein coupled receptor to specifically inhibit an ATP-dependent priming step in the secretory pathway. The effect suggests that the receptor may have an important modulatory role in synaptic transmission.
Bittner
M A
MA
M 1301 MSRB III, Department of Pharmacology, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor 48109, USA. mbittner@umich.edu
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism*; D005089:Exocytosis; D006023:Glycoproteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009479:Neuropeptides; D009489:Neurosecretion / Q000187:drug effects* / Q000502:physiology; D018000:Receptors, Peptide / Q000378:metabolism*; D013111:Spider Venoms / Q000378:metabolism* / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism
D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018000:Receptors, Peptide; D013111:Spider Venoms; C034800:alpha-latrotoxin receptor; C112162:neurexophilin; C020763:alpha-latrotoxin; D002118:Calcium