Author/Editor		Dudanova, Irina; Sedej, Simon; Ahmad, Mohiuddin; Masius, Henriette; Sargsyan, Vardanush; Zhang, Weiqi; Riedel, Dietmar; Angenstein, Frank; Schild, Detlev; Rupnik, Marjan; Missler, Markus
Title		Important contribution of alpha-neurexins to Ca2+ - triggered exocytosis of secretory granules
Type		članek
Source		J Neurosci
Vol. and No.		Letnik 26, št. 41
Publication year		2006
Volume		str. 10599-613
Language		eng
Abstract		Alpha-Neurexins constitute a family of neuronal cell surface molecules that are essential for efficient neurotransmission, because mice lacking two or all three [alpha]-neurexin genes show a severe reduction of synaptic release. Although analyses of alpha-neurexin knock-outs and transgenic rescue animals suggested an involvement of voltage-dependent Ca2+ channels, it remained unclear whether [alpha]-neurexins have a general role in Ca2+ -dependent exocytosis and how they may affect Ca2+ channels. Here we show by membrane capacitance measurements from melanotrophs in acute pituitary gland slices that release from endocrine cellsis diminished by > 50% in adult -neurexin double knock-out and newborn triple knock-out mice. There is a reduction of the cell volume in mutant melanotrophs' however, no ultrastructural changes in size or intracellular distribution of the secretory granules were observed. Recordings of Ca2+ currents from melanotrophs, transfected human embryonic kidney cells, and brainstem neurons reveal that [alpha]-neurexins do not affect the activation or inactivation properties of Ca2+ channels directly but may be responsible for coupling them to release-ready vesicles and metabotropic receptors. Our data support a general and essential role for [alpha]-neurexins in Ca2+ -triggered exocytosis that is similarly important for secretion from neurons and endocrine cells.
Descriptors		PITUITARY GLAND EXOCYTOSIS CALCIUM CELL ADHESION MOLECULES, NEURONAL TRANSFECTION MICE, KNOCKOUT POLYMERASE CHAIN REACTION MICROSCOPY, CONFOCAL PATCH-CLAMP TECHNIQUES