title: TRIM15 is a focal adhesion protein that regulates focal adhesion disassembly.
abstract: Focal adhesions are macromolecular complexes that connect the actin cytoskeleton to the extracellular matrix. Dynamic turnover of focal adhesions is crucial for cell migration. Paxillin is a multi-adaptor protein that plays an important role in regulating focal adhesion dynamics. Here, we identify TRIM15, a member of the tripartite motif protein family, as a paxillin-interacting factor and a component of focal adhesions. TRIM15 localizes to focal contacts in a myosin-II-independent manner by an interaction between its coiled-coil domain and the LD2 motif of paxillin. Unlike other focal adhesion proteins, TRIM15 is a stable focal adhesion component with restricted mobility due to its ability to form oligomers. TRIM15-depleted cells display impaired cell migration and reduced focal adhesion disassembly rates, in addition to enlarged focal adhesions. Thus, our studies demonstrate a cellular function for TRIM15 as a regulatory component of focal adhesion turnover and cell migration.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA pradeep.uchil@yale.edu walther.mothes@yale.edu.
authors.forename: Pradeep D
authors.initials: PD
authors.lastname: Uchil
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Pawliczek
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Tracy D
authors.initials: TD
authors.lastname: Reynolds
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Ding
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Angelika
authors.initials: A
authors.lastname: Hinz
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Munro
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Floyd
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Hamilton
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA Department of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
authors.forename: Joerg
authors.initials: J
authors.lastname: Bewersdorf
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA Departments of Pharmacology and Yale Cancer Center, Yale University, New Haven, CT 06520, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Calderwood
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06536, USA pradeep.uchil@yale.edu walther.mothes@yale.edu.
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D022001:Focal Adhesions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D051379:Mice; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D000070584:Tripartite Motif Proteins
chemical_list: D002352:Carrier Proteins; D006649:Histocompatibility Antigens; D047908:Intracellular Signaling Peptides and Proteins; D051419:Paxillin; C108239:TRIM10 protein, human; C532481:TRIM10 protein, mouse; D000070584:Tripartite Motif Proteins
keywords: Cell migration; Focal adhesion disassembly; Focal adhesions; Paxillin; TRIM E3 ligases; TRIM15