title: A molecular mechanism for the requirement of PAT-4 (integrin-linked kinase (ILK)) for the localization of UNC-112 (Kindlin) to integrin adhesion sites.
abstract: Caenorhabditis elegans muscle cells attach to basement membrane through adhesion plaques. PAT-3 (β-integrin), UNC-112 (kindlin), and PAT-4 (integrin-linked kinase) are associated with these structures. Genetic analysis indicated that PAT-4 is required for UNC-112 to be properly localized. We investigated the molecular basis of this requirement. We show that the cytoplasmic tail of PAT-3 binds to full-length UNC-112 and that the N- and C-terminal halves of UNC-112 bind to each other. We demonstrate competition between the UNC-112 C-terminal half and PAT-4 for binding to the UNC-112 N-terminal half. The D382V mutation results in lack of binding to PAT-4 and lack of localization to adhesion structures. T346A or E349K mutations, which abolish interaction of the N- and C-terminal halves, permit D382V UNC-112 to localize to adhesion structures. The following model is proposed. UNC-112 exists in closed inactive and open active conformations, and upon binding of PAT-4 to the UNC-112 N-terminal half, UNC-112 is converted into the open state, able to bind to PAT-3.
authors: Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
authors: Hiroshi
authors: H
authors: Qadota
authors: Donald G
authors: DG
authors: Moerman
authors: Guy M
authors: GM
authors: Benian
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D020125:Mutation, Missense; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D000099200:Scaffold Protein ILK
chemical_list: D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D017346:Protein Serine-Threonine Kinases; C411729:UNC-112 protein, C elegans; C466238:PAT-4 protein, C elegans; D000099200:Scaffold Protein ILK