title: Moleskin is essential for the formation of the myotendinous junction in Drosophila.
abstract: It is the precise connectivity between skeletal muscles and their corresponding tendon cells to form a functional myotendinous junction (MTJ) that allows for the force generation required for muscle contraction and organismal movement. The Drosophila MTJ is composed of secreted extracellular matrix (ECM) proteins deposited between integrin-mediated hemi-adherens junctions on the surface of muscle and tendon cells. In this paper, we have identified a novel, cytoplasmic role for the canonical nuclear import protein Moleskin (Msk) in Drosophila embryonic somatic muscle attachment. Msk protein is enriched at muscle attachment sites in late embryogenesis and msk mutant embryos exhibit a failure in muscle-tendon cell attachment. Although the muscle-tendon attachment sites are reduced in size, components of the integrin complexes and ECM proteins are properly localized in msk mutant embryos. However, msk mutants fail to localize phosphorylated focal adhesion kinase (pFAK) to the sites of muscle-tendon cell junctions. In addition, the tendon cell specific proteins Stripe (Sr) and activated mitogen-activated protein kinase (MAPK) are reduced in msk mutant embryos. Our rescue experiments demonstrate that Msk is required in the muscle cell, but not in the tendon cells. Moreover, muscle attachment defects due to loss of Msk are rescued by an activated form of MAPK or the secreted epidermal growth factor receptor (Egfr) ligand Vein. Taken together, these findings provide strong evidence that Msk signals non-autonomously through the Vein-Egfr signaling pathway for late tendon cell late differentiation and/or maintenance.
authors.affiliation: Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri, Kansas City, MO 64110, USA.
authors.forename: Ze Cindy
authors.initials: ZC
authors.lastname: Liu
authors.forename: Erika R
authors.initials: ER
authors.lastname: Geisbrecht
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016023:Integrins / Q000378:metabolism; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism*; D009154:Mutation; D020880:Neuregulins / Q000235:genetics / Q000378:metabolism; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism; D013710:Tendons / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016326:Extracellular Matrix Proteins; D016023:Integrins; D028884:Karyopherins; D008164:Luminescent Proteins; C524335:Msk protein, Drosophila; D020880:Neuregulins; D018010:Receptors, Invertebrate Peptide; D014157:Transcription Factors; C096359:sr protein, Drosophila; C102104:vn protein, Drosophila; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases