title: αB-crystallin interacts with and prevents stress-activated proteolysis of focal adhesion kinase by calpain in cardiomyocytes.
abstract: Focal adhesion kinase (FAK) contributes to cellular homeostasis under stress conditions. Here we show that αB-crystallin interacts with and confers protection to FAK against calpain-mediated proteolysis in cardiomyocytes. A hydrophobic patch mapped between helices 1 and 4 of the FAK FAT domain was found to bind to the β4-β8 groove of αB-crystallin. Such an interaction requires FAK tyrosine 925 and is enhanced following its phosphorylation by Src, which occurs upon FAK stimulation. αB-crystallin silencing results in calpain-dependent FAK depletion and in the increased apoptosis of cardiomyocytes in response to mechanical stress. FAK overexpression protects cardiomyocytes depleted of αB-crystallin against the stretch-induced apoptosis. Consistently, load-induced apoptosis is blunted in the hearts from cardiac-specific FAK transgenic mice transiently depleted of αB-crystallin by RNA interference. These studies define a role for αB-crystallin in controlling FAK function and cardiomyocyte survival through the prevention of calpain-mediated degradation of FAK.
authors.affiliation: Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil.
authors.forename: Michelle B M
authors.initials: MB
authors.lastname: Pereira
authors.affiliation: Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil.
authors.forename: Aline M
authors.initials: AM
authors.lastname: Santos
authors.affiliation: Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil.
authors.forename: Danieli C
authors.initials: DC
authors.lastname: Gonçalves
authors.affiliation: Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil.
authors.forename: Alisson C
authors.initials: AC
authors.lastname: Cardoso
authors.affiliation: Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil.
authors.forename: Sílvio R
authors.initials: SR
authors.lastname: Consonni
authors.affiliation: Chemistry Institute, University of Campinas, Campinas, São Paulo 13083-970, Brazil.
authors.forename: Fabio C
authors.initials: FC
authors.lastname: Gozzo
authors.affiliation: Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil.
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Oliveira
authors.affiliation: Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil.
authors.forename: Ana Helena M
authors.initials: AH
authors.lastname: Pereira
authors.affiliation: Chemistry Institute, University of Campinas, Campinas, São Paulo 13083-970, Brazil.
authors.forename: Alana R
authors.initials: AR
authors.lastname: Figueiredo
authors.affiliation: Chemistry Institute, University of Campinas, Campinas, São Paulo 13083-970, Brazil.
authors.forename: Ana O
authors.initials: AO
authors.lastname: Tiroli-Cepeda
authors.affiliation: Chemistry Institute, University of Campinas, Campinas, São Paulo 13083-970, Brazil.
authors.forename: Carlos H I
authors.initials: CH
authors.lastname: Ramos
authors.affiliation: Gleb Wataghin Physics Institute, University of Campinas, Campinas, São Paulo 13083-859, Brazil.
authors.forename: André A
authors.initials: AA
authors.lastname: de Thomaz
authors.affiliation: Gleb Wataghin Physics Institute, University of Campinas, Campinas, São Paulo 13083-859, Brazil.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Cesar
authors.affiliation: 1] Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, São Paulo 13084-971, Brazil [2] Department of Internal Medicine, School of Medicine, University of Campinas, Campinas, São Paulo 13081-970, Brazil.
authors.forename: Kleber G
authors.initials: KG
authors.lastname: Franchini
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis; D002154:Calpain / Q000378:metabolism*; D002470:Cell Survival; D031541:Fluorescence Resonance Energy Transfer; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D006706:Homeostasis; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology*; D010766:Phosphorylation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D038203:alpha-Crystallin B Chain / Q000737:chemistry*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D038203:alpha-Crystallin B Chain; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D002154:Calpain