Post-transcriptional silencing of the Drosophila homolog of human ZASP: a molecular and functional analysis.
In humans, mutations in ZASP (the gene for Z-band alternatively spliced PDZ-motif protein) are associated with dilated cardiomyopathy and left ventricular non-compaction. In particular, mutations in or around the Zasp motif seem to be related to myofibrillar myopathy. Thus, "zaspopathies" include symptoms such as Z-line disgregation, proximal and distal muscle weakness, cardiomyopathies, and peripheral neuropathies. In order to understand the role of ZASP in muscle structure and function, we have performed a molecular characterization of the Drosophila ortholog of human ZASP and a functional analysis following the post-transcriptional silencing of the Drosophila gene. Transcriptional analysis of dzasp has revealed six additional exons, with respect to the known 16, and multiple splice variants. We have produced transgenic lines harboring constructs that, through the use of the UAS/Gal4 binary system, have enabled us to drive dsRNA interference of dzasp in a tissue-specific manner. Knockdown individuals show locomotor defects associated with alterations of muscle structure and ultrastructure, consistent with a role of dzasp specifically in the maintenance of muscular integrity.
Benna
Clara
C
Department of Biology, University of Padova, Padova, Italy.
Peron
Samantha
S
Rizzo
Giorgia
G
Faulkner
Georgine
G
Megighian
Aram
A
Perini
Giuliana
G
Tognon
Giuseppe
G
Valle
Giorgio
G
Reggiani
Carlo
C
Costa
Rodolfo
R
Zordan
Mauro A
MA
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism; D060588:LIM Domain Proteins; D007814:Larva; D008124:Locomotion / Q000235:genetics; D008969:Molecular Sequence Data; D018485:Muscle Fibers, Skeletal / Q000000981:diagnostic imaging / Q000378:metabolism / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014463:Ultrasonography
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; C120696:LDB3 protein, human; D060588:LIM Domain Proteins; D020033:Protein Isoforms; C526450:Zasp52 protein, Drosophila