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The Journal of Neuroscience, October 11, 2006, 26(41):10599-10613; doi:10.1523/JNEUROSCI.1913-06.2006

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Cellular/Molecular
Important Contribution of {alpha}-Neurexins to Ca2+-Triggered Exocytosis of Secretory Granules

Irina Dudanova,1 * Simon Sedej,2 * Mohiuddin Ahmad,1 * Henriette Masius,1 Vardanush Sargsyan,1 Weiqi Zhang,1 Dietmar Riedel,3 Frank Angenstein,4 Detlev Schild,1,5 Marjan Rupnik,2 and Markus Missler1,6

1Center for Physiology and Pathophysiology, Georg-August University, Göttingen D-37073, Germany, 2European Neuroscience Institute Göttingen, Göttingen D-37073, Germany, 3Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen D-37077, Germany, 4Leibniz Institute for Neurobiology, Magdeburg D-39118, Germany, 5German Research Foundation-Research Center of Molecular Physiology of Brain, Göttingen D-37073, Germany, and 6Institute of Anatomy, Westfälische Wilhelms-University, Münster D-48149, Germany

Correspondence should be addressed to Dr. Markus Missler, Institute of Anatomy, Department of Anatomy and Molecular Neuroscience, Westfälische Wilhelms-University, Vesaliusweg 2-4, Münster D-48149, Germany. Email: mmissle1{at}gwdg.de

{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.

Key words: neuroendocrine cells; exocytosis; neurohormones; pituitary gland; melanotrophs; cell adhesion molecules; Ca2+ channels


Received May 4, 2006; revised Sept. 1, 2006; accepted Sept. 5, 2006.

Correspondence should be addressed to Dr. Markus Missler, Institute of Anatomy, Department of Anatomy and Molecular Neuroscience, Westfälische Wilhelms-University, Vesaliusweg 2-4, Münster D-48149, Germany. Email: mmissle1{at}gwdg.de


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