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First published online 17 June 2008
doi: 10.1242/jcs.026906

Journal of Cell Science 121, 2301-2307 (2008)
Published by The Company of Biologists 2008
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Research Article

TRPC6 channels promote dendritic growth via the CaMKIV-CREB pathway

Yilin Tai1, Shengjie Feng1, Ruiliang Ge2, Wanlu Du1, Xiaoxing Zhang1, Zhuohao He1 and Yizheng Wang1,*

1 Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes of Biological Sciences, State Key Laboratory of Neuroscience, The Graduate School, Chinese Academy of Science, 320 Yueyang Road, Shanghai 200031, People's Republic of China
2 Eastern Hepatobiliary Hospital, Shanghai, 200438, People's Republic of China

* Author for correspondence (e-mail: yzwang{at}ion.ac.cn)

Accepted 24 April 2008

The canonical transient receptor potential channels (TRPCs) are Ca2+-permeable nonselective cation channels with various physiological functions. Here, we report that TRPC6, a member of the TRPC family, promotes hippocampal neuron dendritic growth. The peak expression of TRPC6 in rat hippocampus was between postnatal day 7 and 14, a period known to be important for maximal dendritic growth. Overexpression of TRPC6 increased phosphorylation of Ca2+/calmodulin-dependent kinase IV (CaMKIV) and cAMP-response-element binding protein (CREB) and promoted dendritic growth in hippocampal cultures. Downregulation of TRPC6 by short hairpin RNA interference against TRPC6 suppressed phosphorylation of both CaMKIV and CREB and impaired dendritic growth. Expressing a dominant-negative form of CaMKIV or CREB blocked the TRPC6-induced dendritic growth. Furthermore, inhibition of Ca2+ influx suppressed the TRPC6 effect on dendritic growth. Finally, in TRPC6 transgenic mice, the phosphorylation of CaMKIV and CREB was enhanced and the dendritic growth was also increased. In conclusion, TRPC6 promoted dendritic growth via the CaMKIV-CREB pathway. Our results thus revealed a novel role of TRPC6 during the development of the central nervous system (CNS).

Key words: TRPC channels, Dendritic development, Ca2+/calmodulin-dependent kinase IV (CaMKIV), CREB


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TRPC6: channelling dendrite growth

JCS 2008 121: 1403. [Full Text]  





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