Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor.
Brain-derived neurotrophic factor (BDNF) is known to promote neuronal survival and differentiation and to guide axon extension both in vitro and in vivo. The BDNF-induced chemo-attraction of axonal growth cones requires Ca2+ signalling, but how Ca2+ is regulated by BDNF at the growth cone remains largely unclear. Extracellular application of BDNF triggers membrane currents resembling those through TRPC (transient receptor potential canonical) channels in rat pontine neurons and in Xenopus spinal neurons. Here, we report that in cultured cerebellar granule cells, TRPC channels contribute to the BDNF-induced elevation of Ca2+ at the growth cone and are required for BDNF-induced chemo-attractive turning. Several members of the TRPC family are highly expressed in these neurons, and both Ca2+ elevation and growth-cone turning induced by BDNF are abolished by pharmacological inhibition of TRPC channels, overexpression of a dominant-negative form of TRPC3 or TRPC6, or downregulation of TRPC3 expression via short interfering RNA. Thus, TRPC channel activity is essential for nerve-growth-cone guidance by BDNF.
Li
Yan
Y
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Jia
Yi-Chang
YC
Cui
Kai
K
Li
Ning
N
Zheng
Zai-Yu
ZY
Wang
Yi-Zheng
YZ
Yuan
Xiao-Bing
XB
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D015536:Down-Regulation; D004553:Electric Conductivity; D020439:Growth Cones / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D050052:TRPC Cation Channels; D010738:Type C Phospholipases / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D015220:Calcium Channels; D007473:Ion Channels; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D010738:Type C Phospholipases; D002118:Calcium