title: ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2-MRCKα balance.
abstract: Cell migration is a complex process requiring density and rigidity sensing of the microenvironment to adapt cell migratory speed through focal adhesion and actin cytoskeleton regulation. ICAP-1 (also known as ITGB1BP1), a β1 integrin partner, is essential for ensuring integrin activation cycle and focal adhesion formation. We show that ICAP-1 is monoubiquitylated by Smurf1, preventing ICAP-1 binding to β1 integrin. The non-ubiquitylatable form of ICAP-1 modifies β1 integrin focal adhesion organization and interferes with fibronectin density sensing. ICAP-1 is also required for adapting cell migration in response to substrate stiffness in a β1-integrin-independent manner. ICAP-1 monoubiquitylation regulates rigidity sensing by increasing MRCKα (also known as CDC42BPA)-dependent cell contractility through myosin phosphorylation independently of substrate rigidity. We provide evidence that ICAP-1 monoubiquitylation helps in switching from ROCK2-mediated to MRCKα-mediated cell contractility. ICAP-1 monoubiquitylation serves as a molecular switch to coordinate extracellular matrix density and rigidity sensing thus acting as a crucial modulator of cell migration and mechanosensing.
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Anne-Pascale
authors.initials: AP
authors.lastname: Bouin
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kyumurkov
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Régent-Kloeckner
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Ribba
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Faurobert
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Henri-Noël
authors.identifier: 0000-0002-3918-7330
authors.initials: HN
authors.lastname: Fournier
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bourrin-Reynard
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Manet-Dupé
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Oddou
authors.affiliation: CNRS UMR 5309, Grenoble F-38042, France.|Laboratoire Interdisciplinaire de Physique, UMR CNRS, Grenoble 5588, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Balland
authors.affiliation: INSERM U1209, Grenoble F-38042, France.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Planus
authors.affiliation: INSERM U1209, Grenoble F-38042, France Corinne.albiges-rizo@ujf-grenoble.fr.|Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.|CNRS UMR 5309, Grenoble F-38042, France.
authors.forename: Corinne
authors.identifier: 0000-0002-6333-4150
authors.initials: C
authors.lastname: Albiges-Rizo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000737:chemistry / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D065636:Myotonin-Protein Kinase / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005353:Fibronectins; C512603:ICAP-1 protein, mouse; C108257:ITGB1BP1 protein, human; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C498342:SMURF1 protein, human; D044767:Ubiquitin-Protein Ligases; C105518:CDC42BPA protein, human; D065636:Myotonin-Protein Kinase; C515852:ROCK2 protein, human; D054460:rho-Associated Kinases
keywords: Cell contractility; Cell migration; ICAP-1; Integrin; Monoubiquitylation; Rigidity sensing