SALS, a WH2-domain-containing protein, promotes sarcomeric actin filament elongation from pointed ends during Drosophila muscle growth.
Organization of actin filaments into a well-organized sarcomere structure is critical for muscle development and function. However, it is not completely understood how sarcomeric actin/thin filaments attain their stereotyped lengths. In an RNAi screen in Drosophila primary muscle cells, we identified a gene, sarcomere length short (sals), which encodes an actin-binding, WH2 domain-containing protein, required for proper sarcomere size. When sals is knocked down by RNAi, primary muscles display thin myofibrils with shortened sarcomeres and increased sarcomere number. Both loss- and gain-of-function analyses indicate that SALS may influence sarcomere lengths by promoting thin-filament lengthening from pointed ends. Furthermore, the complex localization of SALS and other sarcomeric proteins in myofibrils reveals that the full length of thin filaments is achieved in a two-step process, and that SALS is required for the second elongation phase, most likely because it antagonizes the pointed-end capping protein Tropomodulin.
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. jbai@genetics.med.harvard.edu
Jianwu
J
Bai
John H
JH
Hartwig
Norbert
N
Perrimon
D008841:Actin Cytoskeleton / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004330:Drosophila / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D054792:Muscle, Striated / Q000502:physiology*; D009210:Myofibrils / Q000502:physiology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000494:pharmacology; D012518:Sarcomeres / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C525781:SALS protein, Drosophila