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 l...

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Bibliographic Details
Published in:Nature 2005-04, Vol.434 (7035), p.894-898
Main Authors: Jia, Yi-Chang, Li, Ning, Wang, Yi-zheng, Yuan, Xiao-bing, Cui, Kai, Zheng, Zai-Yu, Li, Yan
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain
Brain-Derived Neurotrophic Factor - pharmacology
Calcium
Calcium - metabolism
Calcium Channels - genetics
Calcium Channels - metabolism
Calcium Signaling - drug effects
Cell Shape - drug effects
Cells, Cultured
Cerebellum - cytology
Down-Regulation
Electric Conductivity
Fundamental and applied biological sciences. Psychology
Growth Cones - drug effects
Growth Cones - metabolism
Humanities and Social Sciences
Humans
Ion Channels - genetics
Ion Channels - metabolism
Ion Transport - drug effects
letter
multidisciplinary
Nervous system
Neurons
Neurotransmitters
Rats
Rats, Sprague-Dawley
Science
Science (multidisciplinary)
TRPC Cation Channels
Type C Phospholipases - metabolism
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature03477