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Asymmetric retraction of growth cone filopodia following focal inactivation of calcineurin

Nature volume 376, pages 686–690 (1995)Cite this article

Abstract

THE neuronal growth cone is thought to be the site of decision making in nerve growth and guidance1,2. 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 neuro-transmitters, increases intracellular calcium1, and artificial manipulations of growth cone calcium levels affect growth cone morphology and neurite outgrowth3. 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 calmodulin4, functions in neurite outgrowth and directed filopodial motility in cultured chick dorsal root ganglia neurons. Cyclosporin A and FK506, inhibitors of calcineurin5, 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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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, 02138, USA

    Howard Y. Chang, Kohtaro Takei, Anne M. Sydor & Daniel G. Jay

  2. Section on Hematology Research and Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota, 55905, USA

    Timothy Born & Frank Rusnak

Authors
  1. Howard Y. Chang
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  2. Kohtaro Takei
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Chang, H., Takei, K., Sydor, A. et al. Asymmetric retraction of growth cone filopodia following focal inactivation of calcineurin. Nature 376, 686–690 (1995). https://doi.org/10.1038/376686a0

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