RT Journal Article SR Electronic T1 Type IV collagen is essential for proper function of integrin-mediated adhesion in Drosophila muscle fibers JF bioRxiv FD Cold Spring Harbor Laboratory SP 318337 DO 10.1101/318337 A1 András A. Kiss A1 Nikoletta Popovics A1 Kiss Márton A1 Zsolt Boldogkői A1 Katalin Csiszár A1 Mátyás Mink YR 2018 UL http://biorxiv.org/content/early/2018/05/09/318337.abstract AB Congenital muscular dystrophy (CMD), a subgroup of myopathies and a genetically and clinically heterogeneous group of inherited muscle disorders is characterized by progressive muscle weakness, fiber size variability, fibrosis, clustered necrotic fibers, and central myonuclei present in regenerating muscle. Type IV collagen (COL4A1) mutations have recently been identified in patients with intracerebral, vascular, renal, ophthalmologic pathologies and congenital muscular dystrophy, consistent with diagnoses of Walker–Warburg Syndrome or Muscle–Eye–Brain disease. Morphological characteristics of muscular dystrophy have also been demonstrated Col4a1 mutant mice. Yet, several aspects of the pathomechanism of COL4A1-associated muscle defects remained largely uncharacterized. Based on the results of genetic, histological, molecular, and biochemical analyses in an allelic series of Drosophila col4a1 mutants, we provide evidence that col4a1 mutations associate with severely compromised muscle fibers within the single-layer striated muscle of the common oviduct, characterized by loss of sarcomere structure, disintegration and streaming of Z-discs, and aberrant integrin expression within the M-discs, indicating an essential role for the COL4A1 protein. Features of altered cytoskeletal phenotype include actin bundles traversing over sarcomere units, amorphous actin aggregates, atrophy and aberrant fiber size. The mutant COL4A1-associated defects appear to recapitulate integrin-mediated adhesion phenotypes observed in Drosophila by RNA-inhibition. Our results provide insight into the mechanistic details of COL4A1-associated muscle disorders and suggest a role for integrin-collagen interaction in the maintenance of sarcomeres.