Cyclic GMP-Gated CNG Channels Function in Sema3A-Induced Growth Cone Repulsion

• Published in: Neuron (Cambridge, Mass.) Vol. 58; no. 5; pp. 694 - 707
• Main Authors: Togashi, Kazunobu, von Schimmelmann, Melanie J., Nishiyama, Makoto, Lim, Chae-Seok, Yoshida, Norihiro, Yun, Bokyoung, Molday, Robert S., Goshima, Yoshio, Hong, Kyonsoo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12-06-2008; Elsevier Limited
• Subjects: 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; Ion Channels - genetics; Ion Channels - physiology; Membrane Potentials - drug effects; Membrane Potentials - physiology; Membrane Potentials - radiation effects; Microinjections; Models, Biological; MOLNEURO; Morpholines - pharmacology; Neurons; Neurons - cytology; Neurons - drug effects; Organic Chemicals - pharmacokinetics; Patch-Clamp Techniques - methods; Peptides - pharmacology; Photoreceptors; Semaphorin-3A - pharmacology; Spinal Cord - cytology; Statistics, Nonparametric; Studies; Time Factors; Transcription, Genetic; Xenopus; Xenopus laevis; MOLNEURO
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2008.03.017

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 Ca
2+ signaling. However, the Ca
2+-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 Ca
2+ 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.