title: Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects.
abstract: Lamins are the major components of nuclear envelope architecture, being required for both the structural and informational roles of the nuclei. Mutations of lamins cause a spectrum of diseases in humans, including muscular dystrophy. We report here that the loss of the A-type lamin gene, lamin C in Drosophila resulted in pupal metamorphic lethality caused by tendon defects, matching the characteristics of human A-type lamin revealed by Emery-Dreifuss muscular dystrophy (EDMD). In tendon cells lacking lamin C activity, overall cell morphology was affected and organization of the spectraplakin family cytoskeletal protein Shortstop which is prominently expressed in tendon cells gradually disintegrated, notably around the nucleus and in a manner correlating well with the degradation of musculature. Furthermore, lamin C null mutants were efficiently rescued by restoring lamin C expression to shortstop-expressing cells, which include tendon cells but exclude skeletal muscle cells. Thus the critical function of A-type lamin C proteins in Drosophila musculature is to maintain proper function and morphology of tendon cells.
authors.affiliation: Department of Chemistry, Faculty of Science, Niigata University, Niigata 950-2181, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Uchino
authors.forename: Yu-Ki
authors.initials: YK
authors.lastname: Nonaka
authors.forename: Tuneyoshi
authors.initials: T
authors.lastname: Horigome
authors.forename: Shin
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D034904:Lamin Type A / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D034881:Nuclear Lamina / Q000378:metabolism* / Q000473:pathology; D059748:Proteolysis; D011679:Pupa / Q000235:genetics / Q000254:growth & development; D013710:Tendons / Q000002:abnormalities* / Q000166:cytology
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D034904:Lamin Type A; D008840:Microfilament Proteins; C440308:lamin C; C450828:shot protein, Drosophila