Article abstract
Nature Neuroscience 10, 559 - 567 (2007)
Published online: 1 April 2007 | doi:10.1038/nn1870
TRPC channels promote cerebellar granule neuron survival
Yichang Jia1,2,3, Jian Zhou1,2,3, Yilin Tai1,2 & Yizheng Wang1
Abstract
Channels formed by the transient receptor potential (TRP) family of proteins have a variety of physiological functions. Here we report that two members of the TRP cation channel (TRPC) subfamily, TRPC3 and 6, protected cerebellar granule neurons (CGNs) against serum deprivation–induced cell death in cultures and promoted CGN survival in rat brain. In CGN cultures, blocking TRPC channels or downregulating TRPC3 or 6 suppressed brain-derived neurotrophic factor (BDNF)–mediated protection, BDNF-triggered intracellular Ca2+ elevation and BDNF-induced CREB activation. By contrast, overexpressing TRPC3 or 6 increased CREB-dependent reporter gene transcription and prevented apoptosis in the neurons deprived of serum, and this protection was blocked by the dominant negative form of CREB. Furthermore, downregulating TRPC3 or 6 induced CGN apoptosis in neonatal rat cerebellum, and this effect was rescued by overexpressing either TRPC3 or 6. Thus, our findings provide in vitro and in vivo evidence that TRPC channels are important in promoting neuronal survival.
- Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes of Biological Sciences, Key Laboratory of Neurobiology, Shanghai 200031, China.
- The Graduate School, Chinese Academy of Science, 320 Yue Yang Road, Shanghai 200031, China.
- These authors contributed equally to this work.
Correspondence to: Yizheng Wang1 e-mail: yzwang@ion.ac.cn
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Something old, something new: BDNF-induced neuron survival requires TRPC channel functionNature Neuroscience News and Views (01 May 2007)
RESEARCH
Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factorNature Letters to Editor (14 Apr 2005)
Tyrosine phosphatase SHP-2 is a mediator of activity-dependent neuronal excitotoxicityThe EMBO Journal Article (26 Jan 2005)
See all 11 matches for Research
