title: The role of focal adhesion anchoring domains of CAS in mechanotransduction.
abstract: CAS is a docking protein, which was shown to act as a mechanosensor in focal adhesions. The unique assembly of structural domains in CAS is important for its function as a mechanosensor. The tension within focal adhesions is transmitted to a stretchable substrate domain of CAS by focal adhesion-targeting of SH3 and CCH domain of CAS, which anchor the CAS protein in focal adhesions. Mechanistic models of the stretching biosensor propose equal roles for both anchoring domains. Using deletion mutants and domain replacements, we have analyzed the relative importance of the focal adhesion anchoring domains on CAS localization and dynamics in focal adhesions as well as on CAS-mediated mechanotransduction. We confirmed the predicted prerequisite of the focal adhesion targeting for CAS-dependent mechanosensing and unraveled the critical importance of CAS SH3 domain in mechanosensing. We further show that CAS localizes to the force transduction layer of focal adhesions and that mechanical stress stabilizes CAS in focal adhesions.
authors.affiliation: BIOCEV at Faculty of Science, Charles University in Prague, Vestec, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Braniš
authors.affiliation: BIOCEV at Faculty of Science, Charles University in Prague, Vestec, Czech Republic.
authors.forename: Csilla
authors.initials: C
authors.lastname: Pataki
authors.affiliation: Biophysics Group, Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Spörrer
authors.affiliation: Biophysics Group, Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Gerum
authors.affiliation: Biophysics Group, Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Mainka
authors.affiliation: BIOCEV at Faculty of Science, Charles University in Prague, Vestec, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Cermak
authors.affiliation: Biophysics Group, Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Goldmann
authors.affiliation: Biophysics Group, Department of Physics, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
authors.affiliation: BIOCEV at Faculty of Science, Charles University in Prague, Vestec, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Brabek
authors.affiliation: BIOCEV at Faculty of Science, Charles University in Prague, Vestec, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rosel
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D050719:Crk-Associated Substrate Protein / Q000737:chemistry* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D050505:Mutant Proteins / Q000737:chemistry; D000072417:Protein Domains; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship
chemical_list: C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins