Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of secretory granules.
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 cells is diminished by >50% in adult alpha-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.
Dudanova
Irina
I
Center for Physiology and Pathophysiology, Georg-August University, Göttingen D-37073, Germany.
Sedej
Simon
S
Ahmad
Mohiuddin
M
Masius
Henriette
H
Sargsyan
Vardanush
V
Zhang
Weiqi
W
Riedel
Dietmar
D
Angenstein
Frank
F
Schild
Detlev
D
Rupnik
Marjan
M
Missler
Markus
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005089:Exocytosis / Q000502:physiology*; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D022142:Secretory Vesicles / Q000378:metabolism*
D015220:Calcium Channels; D006023:Glycoproteins; D009479:Neuropeptides; C112162:neurexophilin; D002118:Calcium