title: Involvement of Girdin in the determination of cell polarity during cell migration.
abstract: Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement.
authors.affiliation: Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ohara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Enomoto
authors.forename: Takuya
authors.initials: T
authors.lastname: Kato
authors.forename: Takahiko
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Mayu
authors.initials: M
authors.lastname: Isotani-Sakakibara
authors.forename: Naoya
authors.initials: N
authors.lastname: Asai
authors.forename: Maki
authors.initials: M
authors.lastname: Ishida-Takagishi
authors.forename: Liang
authors.initials: L
authors.lastname: Weng
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kato
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakumo
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology; D055786:Gene Knockout Techniques; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D017434:Protein Structure, Tertiary; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D033921:Vesicular Transport Proteins; C502451:CCDC88A protein, human; C509689:PARD3 protein, human; C527550:Ccdc88a protein, mouse