title: IPP Complex Reinforces Adhesion by Relaying Tension-Dependent Signals to Inhibit Integrin Turnover.
abstract: Cytoskeleton-mediated forces regulate the assembly and function of integrin adhesions; however, the underlying mechanisms remain unclear. The tripartite IPP complex, comprising ILK, Parvin, and PINCH, mediates the integrin-actin link at Drosophila embryo muscle attachment sites (MASs). Here, we demonstrate a developmentally earlier function for the IPP complex: to reinforce integrin-extracellular matrix (ECM) adhesion in response to tension. In IPP-complex mutants, the integrin-ECM linkage at MASs breaks in response to intense muscle contractility. Mechanistically, the IPP complex is required to relay force-elicited signals that decelerate integrin turnover at the plasma membrane so that the integrin immobile fraction is adequate to withstand tension. Epistasis analysis shows that alleviation of muscle contractility, downregulation of endocytosis, and enhanced integrin binding to the ECM are sufficient to restore integrin-ECM adhesion and maintain integrin-adhesome organization in IPP-complex mutants. Our findings reveal a role for the IPP complex as an essential mechanosensitive regulatory switch of integrin turnover in vivo.
authors.affiliation: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, 11527 Athens, Greece.
authors.forename: Katerina M
authors.initials: KM
authors.lastname: Vakaloglou
authors.affiliation: Department of Biology, University of Patras, 26500 Rio, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Chrysanthis
authors.forename: Maria Anna
authors.initials: MA
authors.lastname: Rapsomaniki
authors.forename: Zoi
authors.lastname: Lygerou
authors.affiliation: Center of Basic Research, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, 11527 Athens, Greece. Electronic address: czervas@bioacademy.gr.
authors.forename: Christos G
authors.initials: CG
authors.lastname: Zervas
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D004705:Endocytosis; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D036681:Fluorescence Recovery After Photobleaching; D016023:Integrins / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D016296:Mutagenesis; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016608:Talin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D016023:Integrins; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D016608:Talin; D014157:Transcription Factors; D000099200:Scaffold Protein ILK; C582272:parvin protein, Drosophila; C495947:stck protein, Drosophila
keywords: endocytosis; integrin-linked kinase; mechanosensing; mechanotransduction