title: PINK1 gene knockdown leads to increased binding of parkin with actin filament.
abstract: Mutations in the PINK1 gene are known to cause early onset familial Parkinson's disease (PD). Genetic fruit fly model studies and rescue experiments with parkin overexpression suggest that PINK1 and parkin are associated via an unidentified mechanism. To gain additional insight into this interaction, we have investigated the impact of PINK1 deficiency on the biological function of parkin using actin filament dynamics. Actin is known to be associated with parkin and is a key regulator of eukaryotic cell death. PINK1 gene knockdown (KD) significantly increased actin aggregation and its binding with parkin. Known PD-related pathological conditions, such as oxidative stress and mitochondrial dysfunction, also increased actin aggregation and parkin binding. PINK1 KD resulted in the increased phosphorylation of cofilin, a protein important for the remodeling of actin filament and neurodegeneration. These results suggest that altered actin dynamics and increased association of parkin with actin filament might underlie the pathological conditions resulting from PINK1 deficiency.
authors.affiliation: Laboratory of Neuroprotection, Division of Life & Pharmaceutical Sciences, Brain Disease Research Institute, College of Pharmacy, Ewha Woman's University, Seoul, South Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.forename: Jin H
authors.initials: JH
authors.lastname: Son
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051379:Mice; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D004298:Dopamine; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein