Assembly of multiple dystrobrevin-containing complexes in the kidney

Dystrophin is the key component in the assembly and maintenance of the dyst rophin-associated protein complex (DPC) in skeletal muscle. In kidney, dyst roglycan, an integral component of the DPC, is involved in kidney epithelia l morphogenesis, suggesting that the DPC is important in linking the extrac ellular matrix to the internal cytoskeleton of kidney epithelia, Here, we h ave investigated the molecular architecture of dystrophin-like protein comp lexes in kidneys from normal and dystrophin-deficient mice, Using isoform-s pecific antibodies, we show that the different cell types that make up the kidney maintain different dystrophin-like complexes. These complexes can be broadly grouped according to their dystrobrevin content: beta-dystrobrevin containing complexes are present at the basal region of renal epithelial c ells, whilst alpha-dystrobrevin-1 containing complexes are found in endothe lial and smooth muscle cells. Furthermore, these complexes are maintained e ven in the absence of all dystrophin isoforms, Thus our data suggest that t he functions and assembly of the dystrophin-like complexes in kidney differ from those in skeletal muscle and implicate a protein other than dystrophi n as the primary molecule in the assembly and maintenance of kidney complex es. Our findings also provide a possible explanation for the lack of kidney pathology in Duchenne muscular dystrophy patients and mice lacking all dys trophin isoforms.