An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling

Soren Impey; Monika Davare; Adam Lasiek; Dale Fortin; Hideaki Ando; Olga Varlamova; Karl Obrietan; Thomas R Soderling; Richard H Goodman; Gary A Wayman

doi:10.1016/j.mcn.2009.10.005

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An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling

Journal article

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An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling

Soren Impey, Monika Davare, Adam Lasiek, Dale Fortin, Hideaki Ando, Olga Varlamova, Karl Obrietan, Thomas R Soderling, Richard H Goodman and Gary A Wayman

Molecular and cellular neurosciences, Vol.43(1), pp.146-156

2010

DOI: https://doi.org/10.1016/j.mcn.2009.10.005

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https://hdl.handle.net/2376/106078

PMCID: PMC2818337

PMID: 19850129

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https://doi.org/10.1016/j.mcn.2009.10.005View

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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 synaptic plasticity remain largely uncharacterized. We show here that the CREB- and activity-regulated microRNA, miR132, is induced during periods of active synaptogenesis. Moreover, miR132 is necessary and sufficient for hippocampal spine formation. Expression of the miR132 target, p250GAP, is inversely correlated with miR132 levels and spinogenesis. Furthermore, knockdown of p250GAP increases spine formation while introduction of a p250GAP mutant unresponsive to miR132 attenuates this activity. Inhibition of miR132 decreases both mEPSC frequency and the number of GluR1-positive spines, while knockdown of p250GAP has the opposite effect. Additionally, we show that the miR132/p250GAP circuit regulates Rac1 activity and spine formation by modulating synapse-specific Kalirin7-Rac1 signaling. These data suggest that neuronal activity regulates spine formation, in part, by increasing miR132 transcription, which in turn activates a Rac1-Pak actin remodeling pathway.

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Title: An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling
Creators: Soren Impey - Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR, USA
Monika Davare - Vollum Institute, Oregon Health and Science University, Portland, OR, USA
Adam Lasiek - Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
Dale Fortin - Vollum Institute, Oregon Health and Science University, Portland, OR, USA
Hideaki Ando - Cell and Developmental Biology, Oregon Health and Science University, Portland, OR, USA
Olga Varlamova - Cell and Developmental Biology, Oregon Health and Science University, Portland, OR, USA
Karl Obrietan - Department of Neuroscience, Ohio State University, Columbus, OH, USA
Thomas R Soderling - Vollum Institute, Oregon Health and Science University, Portland, OR, USA
Richard H Goodman - Vollum Institute, Oregon Health and Science University, Portland, OR, USA
Gary A Wayman - Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA, USA
Publication Details: Molecular and cellular neurosciences, Vol.43(1), pp.146-156
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: Elsevier Inc
Identifiers: 99900546734401842
Language: English
Resource Type: Journal article