title: Functional analysis of parvin and different modes of IPP-complex assembly at integrin sites during Drosophila development.
abstract: Integrin-linked kinase (ILK), PINCH and parvin constitute the tripartite IPP complex that maintains the integrin-actin link at embryonic muscle attachment sites (MASs) in Drosophila. Here we showed that parvin null mutants in Drosophila exhibit defects in muscle adhesion, similar to ILK and PINCH mutants. Furthermore, the identical muscle phenotype of the triple mutant, which for the first time in any organism removed the entire IPP-complex function, genetically demonstrated that parvin, ILK and PINCH function synergistically. This is consistent with the tight localization of the tripartite complex at sites of integrin adhesion, namely MASs in the developing embryo and focal-contact-like structures in the wing epithelium. Parvin contains tandem unconventional calponin-homology (CH) domains separated by a linker sequence, and a less-well conserved N-terminal region. In vivo structure-function analysis revealed that all the domains are essential for parvin function, whereas recruitment at integrin adhesion sites is mediated by two localization signals: one located within the CH2 domain as previously reported, and a second novel signal within the CH1 domain. Interestingly, this site is masked by the linker region between the two CH domains, suggesting a regulatory mechanism to control parvin localization. Finally, whereas in muscles only ILK controls the stability and localization of both PINCH and parvin, in the wing epithelium the three proteins mutually depend on each other. Thus molecular differences exist in the assembly properties of IPP complex in specific tissues during development, where differential modulation of the integrin connection to the cytoskeleton is required.
authors.affiliation: Biomedical Research Foundation, Academy of Athens (BRFAA), Division of Genetics, Athens, Greece.
authors.forename: Katerina M
authors.initials: KM
authors.lastname: Vakaloglou
authors.forename: Maria
authors.initials: M
authors.lastname: Chountala
authors.forename: Christos G
authors.initials: CG
authors.lastname: Zervas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D001665:Binding Sites; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D016023:Integrins / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D029721:Drosophila Proteins; D016023:Integrins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000099200:Scaffold Protein ILK; C582272:parvin protein, Drosophila; C495947:stck protein, Drosophila