An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP
Gary A Wayman1, Monika Davare, Hideaki Ando
1Department of Veterinary Anatomy, Physiology, and Pharmacology, Washington State University, 100 Dairy Road, Pullman, WA 99164, USA. waymang@ohsu.edu
Summary
MicroRNA 132 (miR132) is a key regulator of neuronal plasticity. This study reveals the miR132-p250GAP pathway controls activity-dependent dendrite growth and synapse refinement.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neuronal circuitry development relies on activity-regulated gene expression.
- Transcriptional networks governing synapse plasticity are not fully understood.
Purpose of the Study:
- Investigate the role of microRNA 132 (miR132) in activity-dependent neuronal plasticity.
- Elucidate the molecular mechanisms underlying miR132-mediated synapse growth.
Main Methods:
- Utilized cAMP response element-binding (CREB) protein pathway analysis.
- Employed miR132 introduction and inhibition in hippocampal neurons.
- Performed p250GAP translation inhibition and knockdown studies.
- Conducted experiments with dominant-interfering mutants for Rac signaling analysis.
Main Results:
- miR132 is an activity-dependent gene regulated by CREB.
- miR132 enhances dendrite morphogenesis; its inhibition blocks this effect.
- Neuronal activity suppresses p250GAP translation, mimicking miR132 effects.
- Rac signaling acts downstream of the miR132-p250GAP pathway.
Conclusions:
- The miR132-p250GAP pathway is crucial for activity-dependent structural and functional plasticity.
- miR132 regulates dendrite morphogenesis and synapse refinement.
- This pathway offers insights into neuronal development and plasticity mechanisms.
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