title: Drosophila KASH-domain protein Klarsicht regulates microtubule stability and integrin receptor localization during collective cell migration.
abstract: During collective migration of the Drosophila embryonic salivary gland, cells rearrange to form a tube of a distinct shape and size. Here, we report a novel role for the Drosophila Klarsicht-Anc-Syne Homology (KASH) domain protein Klarsicht (Klar) in the regulation of microtubule (MT) stability and integrin receptor localization during salivary gland migration. In wild-type salivary glands, MTs became progressively stabilized as gland migration progressed. In embryos specifically lacking the KASH domain containing isoforms of Klar, salivary gland cells failed to rearrange and migrate, and these defects were accompanied by decreased MT stability and altered integrin receptor localization. In muscles and photoreceptors, KASH isoforms of Klar work together with Klaroid (Koi), a SUN domain protein, to position nuclei; however, loss of Koi had no effect on salivary gland migration, suggesting that Klar controls gland migration through novel interactors. The disrupted cell rearrangement and integrin localization observed in klar mutants could be mimicked by overexpressing Spastin (Spas), a MT severing protein, in otherwise wild-type salivary glands. In turn, promoting MT stability by reducing spas gene dosage in klar mutant embryos rescued the integrin localization, cell rearrangement and gland migration defects. Klar genetically interacts with the Rho1 small GTPase in salivary gland migration and is required for the subcellular localization of Rho1. We also show that Klar binds tubulin directly in vitro. Our studies provide the first evidence that a KASH-domain protein regulates the MT cytoskeleton and integrin localization during collective cell migration.
authors.affiliation: Department of Biology, Medgar Evers College - CUNY, 1638 Bedford Avenue, Brooklyn, NY 11225, USA. Electronic address: mmyat@mec.cuny.edu.
authors.forename: M M
authors.initials: MM
authors.lastname: Myat
authors.affiliation: Department of Biology, Medgar Evers College - CUNY, 1638 Bedford Avenue, Brooklyn, NY 11225, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Rashmi
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: D
authors.initials: D
authors.lastname: Manna
authors.affiliation: Department of Natural Sciences, LaGuardia Community College - CUNY, Long Island City, NY 11101, USA.
authors.forename: N
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Biology, Medgar Evers College - CUNY, 1638 Bedford Avenue, Brooklyn, NY 11225, USA.
authors.forename: U
authors.initials: U
authors.lastname: Patel
authors.affiliation: Department of Biology, Medgar Evers College - CUNY, 1638 Bedford Avenue, Brooklyn, NY 11225, USA.
authors.forename: M
authors.initials: M
authors.lastname: Galiano
authors.affiliation: Department of Biology, Medgar Evers College - CUNY, 1638 Bedford Avenue, Brooklyn, NY 11225, USA.
authors.forename: K
authors.initials: K
authors.lastname: Zielinski
authors.affiliation: Department of Biology, Medgar Evers College - CUNY, 1638 Bedford Avenue, Brooklyn, NY 11225, USA.
authors.forename: A
authors.initials: A
authors.lastname: Lam
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Welte
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D002465:Cell Movement; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D026901:Membrane Transport Proteins / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D012469:Salivary Glands / Q000196:embryology* / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D016023:Integrins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C401521:klar protein, Drosophila; C554441:koi protein, Drosophila; D000251:Adenosine Triphosphatases; C501874:spas protein, Drosophila; C511153:Rho1 protein, Drosophila; D020741:rho GTP-Binding Proteins
keywords: Collective cell migration; Drosophila; Integrin; KASH; Klarsicht; Microtubule; Morphogenesis; Salivary gland; Tubulin