Abstract
α-Latrotoxin and its plasma membrane receptors cause a number of distinct effects in secretory cells. First, by tethering α-latrotoxin to the plasma membrane, CIRL/latrophilin and neurexin 1α facilitate α-latrotoxin-induced channel formation. The stimulation of secretion by α-latrotoxin in neuroendocrine cells is a consequence of Ca 2+ influx through these α-latrotoxin-induced channels. In addition to channel formation, α-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 α-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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