Slowdown promotes muscle integrity by modulating integrin-mediated adhesion at the myotendinous junction.
The correct assembly of the myotendinous junction (MTJ) is crucial for proper muscle function. In Drosophila, this junction comprises hemi-adherens junctions that are formed upon arrival of muscles at their corresponding tendon cells. The MTJ mainly comprises muscle-specific alphaPS2betaPS integrin receptors and their tendon-derived extracellular matrix ligand Thrombospondin (Tsp). We report the identification and functional analysis of a novel tendon-derived secreted protein named Slowdown (Slow). Homozygous slow mutant larvae exhibit muscle or tendon rupture, sluggish larval movement, partial lethality, and the surviving adult flies are unable to fly. These defects result from improper assembly of the embryonic MTJ. In slow mutants, Tsp prematurely accumulates at muscle ends, the morphology of the muscle leading edge changes and the MTJ architecture is aberrant. Slow was found to form a protein complex with Tsp. This complex is biologically active and capable of altering the morphology and directionality of muscle ends. Our analysis implicates Slow as an essential component of the MTJ, crucial for ensuring muscle and tendon integrity during larval locomotion.
Gilsohn
Eliezer
E
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Volk
Talila
T
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D004330:Drosophila / Q000196:embryology / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D007365:Intercellular Junctions / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D009132:Muscles / Q000196:embryology* / Q000502:physiology; D013710:Tendons / Q000196:embryology* / Q000502:physiology*
D029721:Drosophila Proteins; D016023:Integrins; C497469:slmo protein, Drosophila