title: Lim kinase, a bi-functional effector in injury-induced structural plasticity of synapses.
abstract: The structural plasticity of synaptic terminals contributes to normal nervous system function but also to neural degeneration, in the form of terminal retraction, and regeneration, due to process growth. Synaptic morphological change is mediated through the actin cytoskeleton, which is enriched in axonal and dendritic terminals. Whereas the three RhoGTPases, RhoA, Cdc42 and Rac, function as upstream signaling nodes sensitive to extracellular stimuli, LIMK-cofilin activity serves as a common downstream effector to up-regulate actin turnover, which is necessary for both polymerization and depolymerization. The dual effects of LIMK activity make LIMK a potential target of therapeutic intervention for injury-induced synaptic plasticity, as LIMK inhibition can stabilize actin cytoskeleton and preserve existing structure. This therapeutic benefit of LIMK inhibition has been demonstrated in animal models of injury-induced axon retraction and neuritic sprouting by rod photoreceptors. A better understanding of the regulation of LIMK-cofilin activity and the interaction with the microtubular cytoskeleton may open new ways to promote synaptic regeneration that can benefit neuronal degenerative disease.
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Graduate School of Biomedical Sciences, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Townes-Anderson
keywords: LIMK; RhoGTPases; actin turnover; cofilin; structural plasticity; synaptic degeneration and regeneration