Alpha-latrotoxin and its receptors CIRL (latrophilin) and neurexin 1 alpha mediate effects on secretion through multiple mechanisms |
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Authors: | Bittner M A |
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Institution: | M 1301 MSRB III, Department of Pharmacology, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor 48109, USA. mbittner@umich.edu |
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Abstract: | 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. |
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