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1.  Parvin Overexpression Uncovers Tissue-Specific Genetic Pathways and Disrupts F-Actin to Induce Apoptosis in the Developing Epithelia in Drosophila 
PLoS ONE  2012;7(10):e47355.
Parvin is a putative F-actin binding protein important for integrin-mediated cell adhesion. Here we used overexpression of Drosophila Parvin to uncover its functions in different tissues in vivo. Parvin overexpression caused major defects reminiscent of metastatic cancer cells in developing epithelia, including apoptosis, alterations in cell shape, basal extrusion and invasion. These defects were closely correlated with abnormalities in the organization of F-actin at the basal epithelial surface and of integrin-matrix adhesion sites. In wing epithelium, overexpressed Parvin triggered increased Rho1 protein levels, predominantly at the basal side, whereas in the developing eye it caused a rough eye phenotype and severely disrupted F-actin filaments at the retina floor of pigment cells. We identified genes that suppressed these Parvin-induced dominant effects, depending on the cell type. Co-expression of both ILK and the apoptosis inhibitor DIAP1 blocked Parvin-induced lethality and apoptosis and partially ameliorated cell delamination in epithelia, but did not rescue the elevated Rho1 levels, the abnormal organization of F-actin in the wing and the assembly of integrin-matrix adhesion sites. The rough eye phenotype was suppressed by coexpression of either PTEN or Wech, or by knock-down of Xrp1. Two main conclusions can be drawn from our studies: (1), high levels of cytoplasmic Parvin are toxic in epithelial cells; (2) Parvin in a dose dependent manner affects the organization of actin cytoskeleton in both wing and eye epithelia, independently of its role as a structural component of the ILK-PINCH-Parvin complex that mediates the integrin-actin link. Thus, distinct genetic interactions of Parvin occur in different cell types and second site modifier screens are required to uncover such genetic circuits.
doi:10.1371/journal.pone.0047355
PMCID: PMC3471835  PMID: 23077599
2.  Parvin-ILK 
Bioarchitecture  2012;2(3):91-94.
Integrin-linked kinase (ILK), PINCH and Parvin proteins form the IPP-complex that has been established as a core component of the integrin-actin link. Our recent genetic studies on Drosophila parvin, reveal that loss of function mutant defects phenocopy those observed upon loss of ILK or PINCH in the muscle and the wing, strengthening the notion that these proteins function together in the organism. Our work identified that ILK is necessary and sufficient for parvin subcellular localization, corroborating previous data indicating a direct association between these two proteins. Further genetic epistasis analysis of the IPP-complex assembly at integrin adhesion sites reveals that depending on the cell context each component is required differently. At the muscle attachment sites of the embryo, ILK is placed upstream in the hierarchy of genetic interactions required for the IPP-complex assembly. By contrast, in the wing epithelium the three proteins are mutually interdependent. Finally, we uncovered a novel property for the CH1-domain of parvin: its recruitment at the integrin-containing junctions in an ILK-dependent manner. Apparently, this ability of the CH1-domain is controlled by the inter-CH linker region. Thus, an intramolecular interaction within parvin could serve as a putative regulatory mechanism controlling the ILK-Parvin interaction.
doi:10.4161/bioa.20700
PMCID: PMC3414386  PMID: 22880148
integrin; cell adhesion; PINCH; actin; Drosophila

Results 1-2 (2)