XTRPC1-dependent chemotropic guidance of neuronal growth cones.
Calcium arising through release from intracellular stores and from influx across the plasma membrane is essential for signalling by specific guidance cues and by factors that inhibit axon regeneration. The mediators of calcium influx in these cases are largely unknown. Transient receptor potential channels (TRPCs) belong to a superfamily of Ca2+-permeable, receptor-operated channels that have important roles in sensing and responding to changes in the local environment. Here we report that XTRPC1, a Xenopus homolog of mammalian TRPC1, is required for proper growth cone turning responses of Xenopus spinal neurons to microscopic gradients of netrin-1, brain-derived neurotrophic factor and myelin-associated glycoprotein, but not to semaphorin 3A. Furthermore, XTRPC1 is required for midline guidance of axons of commissural interneurons in the developing Xenopus spinal cord. Thus, members of the TRPC family may serve as a key mediator for the Ca2+ influx that regulates axon guidance during development and inhibits axon regeneration in adulthood.
Shim
Sangwoo
S
Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, Maryland 21205, USA.
Goh
Eyleen L
EL
Ge
Shaoyu
S
Sailor
Kurt
K
Yuan
Joseph P
JP
Roderick
H Llewelyn
HL
Bootman
Martin D
MD
Worley
Paul F
PF
Song
Hongjun
H
Ming
Guo-li
GL
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004625:Embryo, Nonmammalian; D007839:Functional Laterality / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006131:Growth Inhibitors / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D000075388:Netrin-1; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D050052:TRPC Cation Channels; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000494:pharmacology; D029867:Xenopus Proteins / Q000187:drug effects / Q000378:metabolism*; D014982:Xenopus laevis
D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D006131:Growth Inhibitors; D018992:Myelin-Associated Glycoprotein; D009414:Nerve Growth Factors; D050052:TRPC Cation Channels; C502469:TRPC1 protein, Xenopus; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; C096351:transient receptor potential cation channel, subfamily C, member 1; D000075388:Netrin-1