Asymmetric retraction of growth cone filopodia following focal inactivation of calcineurin

Nature
H Y ChangDaniel G Jay

Abstract

The neuronal growth cone is thought to be the site of decision making in nerve growth and guidance. One likely mechanism of how the growth cone translates various extracellular cues into directed motility involves rises in intracellular calcium. A variety of physiological cues, such as adhesion molecules and neurotransmitters, increases intracellular calcium, and artificial manipulations of growth cone calcium levels affect growth cone morphology and neurite outgrowth. The molecular events downstream of calcium fluxes are incompletely understood. Here we show that calcineurin, a protein phosphatase enriched in growth cones that is dependent on calcium ions and calmodulin, functions in neurite outgrowth and directed filopodial motility in cultured chick dorsal root ganglia neurons. Cyclosporin A and FK506, inhibitors of calcineurin, delayed neuritogenesis and inhibited neurite extension. Chromophore-assisted laser inactivation of calcineurin in regions of growth cones causes localized filopodial and lamellipodial retraction and influences the direction of subsequent outgrowth. We suggest that a spatial distribution of calcineurin activity within the growth cone can regulate motility and direct outgrowth.

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Citations

Jan 29, 2000·Microscopy Research and Technique·A Buchstaller, D G Jay
Jul 13, 1999·Cell Motility and the Cytoskeleton·C W LiuD G Jay
Feb 19, 1998·Journal of Neurobiology·V Rehder, S Cheng
Mar 14, 2002·Journal of Neurobiology·Su ChengVincent Rehder
Mar 21, 2001·Journal of Neurobiology·Y S KimM F VanBerkum
Feb 11, 1998·Molecular Neurobiology·B G Gold
Jul 27, 2012·Neuroscience Bulletin·Wei LiGuangshuo Ou
Nov 19, 2003·Neural Networks : the Official Journal of the International Neural Network Society·Shinichi KikuchiMasaru Tomita
Oct 29, 2003·Biophysical Journal·Feng-Song WangDaniel G Jay
Sep 23, 2003·Brain Research. Molecular Brain Research·Mitch PriceJonathan R Day
May 13, 1999·Progress in Neurobiology·M MoriokaE Miyamoto
Oct 21, 1999·Biochimica Et Biophysica Acta·D G Jay, T Sakurai
Apr 22, 1999·General Pharmacology·S HarrisonD Spina
Jan 12, 2002·Current Opinion in Pharmacology·Bruce G Gold, John G Nutt
Nov 13, 2002·The Journal of Biological Chemistry·Ehrin N JohnsonJoyce Bischoff
May 8, 1999·Molecular Biology of the Cell·L Castelo, D G Jay
Jan 27, 2004·Molecular Biology of the Cell·L'ubica AdamíkováGero Steinberg
Sep 16, 2011·Regenerative Medicine·Edward C TollMartin A Birchall
May 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T SurreyS Leibler
Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·M S HalfonH Keshishian
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·J KudlaS Luan
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·D Grate, C Wilson
Nov 10, 2004·Proceedings of the National Academy of Sciences of the United States of America·Bryan KaehrJason B Shear
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Jan 16, 2007·Journal of Neurochemistry·Ji-Eun LeeHong-Duk Youn
Aug 2, 2011·Journal of Cellular and Molecular Medicine·Virginie DescazeaudMarie Essig

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