Cyclic GMP-gated CNG channels function in Sema3A-induced growth cone repulsion.
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.
Togashi
Kazunobu
K
Department of Biochemistry, New York University School of Medicine, New York, NY 10016-6402, USA.
von Schimmelmann
Melanie J
MJ
Nishiyama
Makoto
M
Lim
Chae-Seok
CS
Yoshida
Norihiro
N
Yun
Bokyoung
B
Molday
Robert S
RS
Goshima
Yoshio
Y
Hong
Kyonsoo
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D020439:Growth Cones / Q000187:drug effects*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008845:Microinjections; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009930:Organic Chemicals / Q000493:pharmacokinetics; D018408:Patch-Clamp Techniques / Q000379:methods; D010455:Peptides / Q000494:pharmacology; D040121:Semaphorin-3A / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology; D018709:Statistics, Nonparametric; D013997:Time Factors; D014158:Transcription, Genetic; D014982:Xenopus laevis
D002352:Carrier Proteins; D054815:Cyclic Nucleotide-Gated Cation Channels; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; D009025:Morpholines; C403124:Oregon Green BAPTA-dextran; D009930:Organic Chemicals; D010455:Peptides; C121720:SNP-1 protein, synthetic; D040121:Semaphorin-3A; D006152:Cyclic GMP; D002118:Calcium