title: Cbl-associated protein regulates assembly and function of two tension-sensing structures in Drosophila.
abstract: Cbl-associated protein (CAP) localizes to focal adhesions and associates with numerous cytoskeletal proteins; however, its physiological roles remain unknown. Here, we demonstrate that Drosophila CAP regulates the organization of two actin-rich structures in Drosophila: muscle attachment sites (MASs), which connect somatic muscles to the body wall; and scolopale cells, which form an integral component of the fly chordotonal organs and mediate mechanosensation. Drosophila CAP mutants exhibit aberrant junctional invaginations and perturbation of the cytoskeletal organization at the MAS. CAP depletion also results in collapse of scolopale cells within chordotonal organs, leading to deficits in larval vibration sensation and adult hearing. We investigate the roles of different CAP protein domains in its recruitment to, and function at, various muscle subcellular compartments. Depletion of the CAP-interacting protein Vinculin results in a marked reduction in CAP levels at MASs, and vinculin mutants partially phenocopy Drosophila CAP mutants. These results show that CAP regulates junctional membrane and cytoskeletal organization at the membrane-cytoskeletal interface of stretch-sensitive structures, and they implicate integrin signaling through a CAP/Vinculin protein complex in stretch-sensitive organ assembly and function.
authors.affiliation: Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205,  USA.
authors.forename: Rajnish
authors.initials: R
authors.lastname: Bharadwaj
authors.forename: Madhuparna
authors.initials: M
authors.lastname: Roy
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ohyama
authors.forename: Elena
authors.initials: E
authors.lastname: Sivan-Loukianova
authors.forename: Michael
authors.initials: M
authors.lastname: Delannoy
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lloyd
authors.forename: Marta
authors.initials: M
authors.lastname: Zlatic
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Eberl
authors.forename: Alex L
authors.initials: AL
authors.lastname: Kolodkin
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000502:physiology; D000595:Amino Acid Sequence; D000825:Animal Structures / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D021982:Cell-Matrix Junctions / Q000378:metabolism / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055724:Electrophysiological Phenomena; D018507:Gene Expression Regulation, Developmental; D049750:Genome, Insect; D006311:Hearing Disorders / Q000235:genetics / Q000473:pathology / Q000662:veterinary; D016023:Integrins / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D040542:Mechanotransduction, Cellular; D046529:Microscopy, Electron, Transmission; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D025941:Protein Interaction Mapping; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D016608:Talin / Q000235:genetics / Q000378:metabolism; D014732:Vibration; D016596:Vinculin / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D003598:Cytoskeletal Proteins; D016023:Integrins; D046912:Multiprotein Complexes; D016608:Talin; D016596:Vinculin