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Dudanova, I; Sedej, S; Ahmad, M; Masius, H; Sargsyan, V; Zhang, W; Riedel, D; Angenstein, F; Schild, D; Rupnik, M; Missler, M.
Important contribution of alpha-neurexins to Ca2+-triggered exocytosis of secretory granules.
J Neurosci. 2006; 26(41):10599-10613
Doi: 10.1523/JNEUROSCI.1913-06.2006
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- Führende Autor*innen der Med Uni Graz
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Sedej Simon
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- 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 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.
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Animals -
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Calcium - metabolism
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Calcium Channels - genetics
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Cell Line - genetics
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Exocytosis - physiology
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Glycoproteins - deficiency
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Humans - deficiency
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Mice - deficiency
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Mice, Knockout - deficiency
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Neuropeptides - deficiency
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Secretory Vesicles - metabolism
- Find related publications in this database (Keywords)
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neuroendocrine cells
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exocytosis
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neurohormones
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pituitary gland
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melanotrophs
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cell adhesion molecules
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Ca2+ channels