한빛사논문
Abstract
1 Department of Biochemistry, New York University School of Medicine,
New York, NY 10016-6402, USA
2 Department of Biochemistry and
Molecular Biology, Faculty of Medicine, University of British Columbia, Vancouver,
BC V6T 1Z3, Canada
3 Department of Molecular Pharmacology and
Neurobiology, Yokohama City University School of Medicine, Yokohama 236-0004,
Japan
*Corresponding author
Kyonsoo Hong
Summary
Cyclic nucleotide-gated channels (CNGCs) transduce external signals required for sensory processes, e.g., photoreception, olfaction, and taste. Nerve growth cone guidance by diffusible attractive and repulsive molecules is regulated by differential growth cone Ca2+ signaling. However, the Ca2+-conducting ion channels that transduce guidance molecule signals are largely unknown. We show that rod-type CNGC-like channels function in the repulsion of cultured Xenopus spinal neuron growth cones by Sema3A, which triggers the production of the cGMP that activates the Xenopus CNGA1 (xCNGA1) subunit-containing channels in interneurons. Downregulation of xCNGA1 or overexpression of a mutant xCNGA1 incapable of binding cGMP abolished CNG currents and converted growth cone repulsion to attraction in response to Sema3A. We also show that Ca2+ entry through xCNGCs is required to mediate the repulsive Sema3A signal. These studies extend our knowledge of the function of CNGCs by demonstrating their requirement for signal transduction in growth cone guidance.
Footnotes4 These authors contributed equally to this work.
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