title: Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity.
abstract: Precise regulation of the dendritic spine actin cytoskeleton is critical for neurodevelopment and neuronal plasticity, but how neurons spatially control actin dynamics is not well defined. Here, we identify direct palmitoylation of the actin regulator LIM kinase-1 (LIMK1) as a novel mechanism to control spine-specific actin dynamics. A conserved palmitoyl-motif is necessary and sufficient to target LIMK1 to spines and to anchor LIMK1 in spines. ShRNA knockdown/rescue experiments reveal that LIMK1 palmitoylation is essential for normal spine actin polymerization, for spine-specific structural plasticity and for long-term spine stability. Palmitoylation is critical for LIMK1 function because this modification not only controls LIMK1 targeting, but is also essential for LIMK1 activation by its membrane-localized upstream activator PAK. These novel roles for palmitoylation in the spatial control of actin dynamics and kinase signaling provide new insights into structural plasticity mechanisms and strengthen links between dendritic spine impairments and neuropathological conditions.
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, United States.
authors.forename: Joju
authors.initials: J
authors.lastname: George
authors.affiliation: Heart and Stroke Partnership for Stroke Recovery, University of Ottawa, Ottawa, Canada.
authors.forename: Cary
authors.initials: C
authors.lastname: Soares
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, United States.
authors.forename: Audrey
authors.initials: A
authors.lastname: Montersino
authors.affiliation: Heart and Stroke Partnership for Stroke Recovery, University of Ottawa, Ottawa, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Beique
authors.affiliation: Shriners Hospitals Pediatric Research Center, Temple University School of Medicine, Philadelphia, United States.
authors.forename: Gareth M
authors.initials: GM
authors.lastname: Thomas
mesh_terms: D000199:Actins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D054461:Lim Kinases / Q000378:metabolism*; D054878:Lipoylation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational
chemical_list: D000199:Actins; C515892:LIMK1 protein, human; D054461:Lim Kinases
keywords: DHHC; LIMK1; LTP; dendritic spines; glutamate; neuroscience; protein trafficking; rat