Cyclic GMP-gated CNG channels function in Sema3A-induced growth cone repulsion

Kazunobu Togashi; Melanie J von Schimmelmann; Makoto Nishiyama; Chae-Seok Lim; Norihiro Yoshida; Bokyoung Yun; Robert S Molday; Yoshio Goshima; Kyonsoo Hong

doi:10.1016/j.neuron.2008.03.017

Cyclic GMP-gated CNG channels function in Sema3A-induced growth cone repulsion

Neuron. 2008 Jun 12;58(5):694-707. doi: 10.1016/j.neuron.2008.03.017.

Authors

Kazunobu Togashi¹, Melanie J von Schimmelmann, Makoto Nishiyama, Chae-Seok Lim, Norihiro Yoshida, Bokyoung Yun, Robert S Molday, Yoshio Goshima, Kyonsoo Hong

Affiliation

¹ Department of Biochemistry, New York University School of Medicine, New York, NY 10016-6402, USA.

PMID: 18549782
DOI: 10.1016/j.neuron.2008.03.017

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism
Calcium Signaling / drug effects
Calcium Signaling / physiology
Carrier Proteins / pharmacology
Cyclic GMP / physiology*
Cyclic Nucleotide-Gated Cation Channels / genetics
Cyclic Nucleotide-Gated Cation Channels / physiology*
Embryo, Nonmammalian
Growth Cones / drug effects*
In Vitro Techniques
Intercellular Signaling Peptides and Proteins
Ion Channels / genetics
Ion Channels / physiology*
Membrane Potentials / drug effects
Membrane Potentials / physiology
Membrane Potentials / radiation effects
Microinjections
Models, Biological
Morpholines / pharmacology
Neurons / cytology*
Neurons / drug effects
Organic Chemicals / pharmacokinetics
Patch-Clamp Techniques / methods
Peptides / pharmacology
Semaphorin-3A / pharmacology*
Spinal Cord / cytology
Statistics, Nonparametric
Time Factors
Transcription, Genetic
Xenopus laevis

Substances

Carrier Proteins
Cyclic Nucleotide-Gated Cation Channels
Intercellular Signaling Peptides and Proteins
Ion Channels
Morpholines
Oregon Green BAPTA-dextran
Organic Chemicals
Peptides
SNP-1 protein, synthetic
Semaphorin-3A
Cyclic GMP
Calcium