title: Centrosomal AKAP350 and CIP4 act in concert to define the polarized localization of the centrosome and Golgi in migratory cells.
abstract: The acquisition of a migratory phenotype is central in processes as diverse as embryo differentiation and tumor metastasis. An early event in this phenomenon is the generation of a nucleus-centrosome-Golgi back-to-front axis. AKAP350 (also known as AKAP9) is a Golgi and centrosome scaffold protein that is involved in microtubule nucleation. AKAP350 interacts with CIP4 (also known as TRIP10), a cdc42 effector that regulates actin dynamics. The present study aimed to characterize the participation of centrosomal AKAP350 in the acquisition of migratory polarity, and the involvement of CIP4 in the pathway. The decrease in total or in centrosomal AKAP350 led to decreased formation of the nucleus-centrosome-Golgi axis and defective cell migration. CIP4 localized at the centrosome, which was enhanced in migratory cells, but inhibited in cells with decreased centrosomal AKAP350. A decrease in the CIP4 expression or inhibition of the CIP4-AKAP350 interaction also led to defective cell polarization. Centrosome positioning, but not nuclear movement, was affected by loss of CIP4 or AKAP350 function. Our results support a model in which AKAP350 recruits CIP4 to the centrosome, providing a centrosomal scaffold to integrate microtubule and actin dynamics, thus enabling centrosome polarization and ensuring cell migration directionality.
authors.affiliation: Instituto de Fisiología Experimental, Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario 2000, Argentina.
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Tonucci
authors.affiliation: Instituto de Fisiología Experimental, Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario 2000, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Hidalgo
authors.affiliation: Instituto de Fisiología Experimental, Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario 2000, Argentina.
authors.forename: Anabela
authors.initials: A
authors.lastname: Ferretti
authors.affiliation: Instituto de Fisiología Experimental, Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario 2000, Argentina.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Almada
authors.affiliation: Instituto de Fisiología Experimental, Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario 2000, Argentina.
authors.forename: Cristián
authors.initials: C
authors.lastname: Favre
authors.affiliation: Department of Surgery, Epithelial Biology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center and the Nashville VA Medical Center, Nashville, TN 37232, USA Department of Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center and the Nashville VA Medical Center, Nashville, TN 37232, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
authors.affiliation: Department of Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center and the Nashville VA Medical Center, Nashville, TN 37232, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Kaverina
authors.affiliation: Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde (IIB-INTECH), Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín 1650, Buenos Aires, Argentina.
authors.forename: Arlinet
authors.initials: A
authors.lastname: Kierbel
authors.affiliation: Instituto de Fisiología Experimental, Consejo de Investigaciones Científicas y Técnicas, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario 2000, Argentina larocca@ifise-conicet.gov.ar.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Larocca
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D015778:Minor Histocompatibility Antigens
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; C406285:TRIP10 protein, human
keywords: AKAP350; AKAP450; Actin; CIP4; Centrosome; Migratory polarity