Journal article
An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP
Proceedings of the National Academy of Sciences - PNAS, Vol.105(26), pp.9093-9098
07/01/2008
Handle:
https://hdl.handle.net/2376/105000
PMCID: PMC2449370
PMID: 18577589
Abstract
Activity-regulated gene expression is believed to play a key role in the development and refinement of neuronal circuitry. Nevertheless, the transcriptional networks that regulate synapse growth and plasticity remain largely uncharacterized. Here, we show that microRNA 132 (miR132) is an activity-dependent rapid response gene regulated by the cAMP response element-binding (CREB) protein pathway. Introduction of miR132 into hippocampal neurons enhanced dendrite morphogenesis whereas inhibition of miR132 by 2′
O
-methyl RNA antagonists blocked these effects. Furthermore, neuronal activity inhibited translation of p250GAP, a miR132 target, and siRNA-mediated knockdown of p250GAP mimicked miR132-induced dendrite growth. Experiments using dominant-interfering mutants suggested that Rac signaling is downstream of miR132 and p250GAP. We propose that the miR132–p250GAP pathway plays a key role in activity-dependent structural and functional plasticity.
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Details
- Title
- An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP
- Creators
- Gary A Wayman - Department of Veterinary Anatomy, Physiology, and Pharmacology, Washington State University, 100 Dairy Road, Pullman, WA 99164Monika Davare - Vollum InstituteHideaki Ando - Oregon Stem Cell Center, andDale Fortin - Vollum InstituteOlga Varlamova - Oregon Stem Cell Center, andHai-Ying M Cheng - Department of Neuroscience, Ohio State University, Columbus, OH 43210Daniel Marks - Center for Study of Weight Regulation, Oregon Health and Science University, 3181 Sam Jackson Park Road, Portland, OR 97239; andKarl Obrietan - Department of Neuroscience, Ohio State University, Columbus, OH 43210Thomas R Soderling - Vollum InstituteRichard H Goodman - Vollum InstituteSoren Impey - Cell and Developmental Biology
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.105(26), pp.9093-9098
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- National Academy of Sciences
- Identifiers
- 99900546868801842
- Language
- English
- Resource Type
- Journal article