Journal
MOLECULAR AND CELLULAR NEUROSCIENCE
Volume 75, Issue -, Pages 14-26Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2016.06.002
Keywords
Dendrites; Spines; Synapse; Chimaerin; Long-term potentiation
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Funding
- Alfred P. Sloan Foundation [FG-BR-5098]
- Hartwell Foundation
- Basil O'Connor Starter Scholar Research Award
- National Institute of Neurological Disorders and Stroke [R01NS094678-01A1]
- National Science Foundation Graduate Research Fellowship [DGE1256260]
- University of Michigan Rackham Merit Fellowship
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Dendritic spines are fine neuronal processes where spatially restricted input can induce activity-dependent changes in one spine, while leaving neighboring spines unmodified. Morphological spine plasticity is critical for synaptic transmission and is thought to underlie processes like learning and memory. Significantly, defects in dendritic spine stability and morphology are common pathogenic features found in several neurodevelopmental and neuropsychiatric disorders. The remodeling of spines relies on proteins that modulate the underlying cytoslceleton, which is primarily composed of filamentous (F)-actin. The Rho-GTPase Rac1 is a major regulator of F-actin and is essential for the development and plasticity of dendrites and spines. However, the key molecules and mechanisms that regulate Rac1-dependent pathways at spines and synapses are not well understood. We have identified the Rac1-GTPase activating protein, alpha 2-chimaerin, as a critical negative regulator of Rac1 in hippocampal neurons. The loss of a2-chimaerin significantly increases the levels of active Rac1 and induces the formation of aberrant polymorphic dendritic spines. Further, disruption of alpha 2-chimaerin signaling simplifies dendritic arbor complexity and increases the presence of dendritic spines that appear poly-innervated. Our data suggests that alpha 2-chimaerin serves as a brake to constrain Rac1-dependent signaling to ensure that the mature morphology of spines is maintained in response to network activity. (C) 2016 Elsevier Inc. All rights reserved.
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