title: Prickle1 promotes focal adhesion disassembly in cooperation with the CLASP-LL5β complex in migrating cells.
abstract: Prickle is known to be involved in planar cell polarity, including convergent extension and cell migration; however, the detailed mechanism by which Prickle regulates cellular functions is not well understood. Here, we show that Prickle1 regulates front-rear polarization and migration of gastric cancer MKN1 cells. Prickle1 preferentially accumulated at the cell retraction site in close proximity to paxillin at focal adhesions. Prickle1 dynamics correlated with those of paxillin during focal adhesion disassembly. Furthermore, Prickle1 was required for focal adhesion disassembly. CLASPs (of which there are two isoforms, CLASP1 and CLASP2, in mammals) and LL5β (also known as PHLDB2) have been reported to form a complex at cell edges and to control microtubule-dependent focal adhesion disassembly. Prickle1 was associated with CLASPs and LL5β, and was required for the LL5β-dependent accumulation of CLASPs at the cell edge. Knockdown of CLASPs and LL5β suppressed Prickle1-dependent cell polarization and migration. Prickle1 localized to the membrane through its farnesyl moiety, and the membrane localization was necessary for Prickle1 to regulate migration, to bind to CLASPs and LL5β, and to promote microtubule targeting of focal adhesions. Taken together, these results suggest that Prickle1 promotes focal adhesion disassembly during the retraction processes of cell polarization and migration.
authors.affiliation: Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Boon Cheng
authors.initials: BC
authors.lastname: Lim
authors.affiliation: Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsumoto
authors.affiliation: Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan WPI-Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Mizuno
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan WPI-Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita, Osaka 565-0871, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kikuta
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan WPI-Immunology Frontier Research Center, Osaka University, Yamadaoka 3-1, Suita, Osaka 565-0871, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan akikuchi@molbiobc.med.osaka-u.ac.jp.
authors.forename: Akira
authors.identifier: 0000-0003-3378-9522
authors.initials: A
authors.lastname: Kikuchi
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C497850:CLASP1 protein, human; C497851:CLASP2 protein, human; D002352:Carrier Proteins; D060588:LIM Domain Proteins; D008869:Microtubule-Associated Proteins; C471180:PHLDB2 protein, human; C515173:PRICKLE1 protein, human; D025521:Tumor Suppressor Proteins; D004815:Epidermal Growth Factor
keywords: CLASP; Focal adhesion; LL5β; Migration; Polarity; Prickle