Altered stress fibers and integrin expression in the Malpighian epithelium of Drosophila type IV collagen mutants.

Basement membranes (BMs) are highly specialized extracellular matrices (ECMs) that provide support and polarization cues for epithelial cells. Proper adhesion to the BM is pivotal in epithelial cell function and survival. Type IV collagens are the predominant components of all types of BMs, that form an irregular, polygonal lattice and serve as a scaffold for numerous other BM components and BM-associated cells. Mutations in the ubiquitous human BM components COL4A1 and COL4A2 cause a multisystem disorder involving nephropathy. Affected patients develop renal dysfunction and chronic kidney failure with or without hematuria. Mouse Col4a1 and Col4a2 mutants recapitulate the human symptoms. In vertebrates, excretion is accomplished by the kidneys and by the Malpighian tubules in insects, including the fruit fly Drosophila. Our present results with dominant, temperature-sensitive mutation of the Drosophila col4a1 gene demonstrate altered integrin expression and amplified effects of mechanical stress on the Malpighian epithelial cytoskeleton.