title: The role of Drosophila Lamin C in muscle function and gene expression.
abstract: The inner side of the nuclear envelope (NE) is lined with lamins, a meshwork of intermediate filaments that provides structural support for the nucleus and plays roles in many nuclear processes. Lamins, classified as A- or B-types on the basis of biochemical properties, have a conserved globular head, central rod and C-terminal domain that includes an Ig-fold structural motif. In humans, mutations in A-type lamins give rise to diseases that exhibit tissue-specific defects, such as Emery-Dreifuss muscular dystrophy. Drosophila is being used as a model to determine tissue-specific functions of A-type lamins in development, with implications for understanding human disease mechanisms. The GAL4-UAS system was used to express wild-type and mutant forms of Lamin C (the presumed Drosophila A-type lamin), in an otherwise wild-type background. Larval muscle-specific expression of wild type Drosophila Lamin C caused no overt phenotype. By contrast, larval muscle-specific expression of a truncated form of Lamin C lacking the N-terminal head (Lamin C DeltaN) caused muscle defects and semi-lethality, with adult 'escapers' possessing malformed legs. The leg defects were due to a lack of larval muscle function and alterations in hormone-regulated gene expression. The consequences of Lamin C association at a gene were tested directly by targeting a Lamin C DNA-binding domain fusion protein upstream of a reporter gene. Association of Lamin C correlated with localization of the reporter gene at the nuclear periphery and gene repression. These data demonstrate connections among the Drosophila A-type lamin, hormone-induced gene expression and muscle function.
authors: Department of Biochemistry, University of Iowa, Iowa City, IA 52241, USA.
authors: George
authors: G
authors: Dialynas
authors: Sean
authors: S
authors: Speese
authors: Vivian
authors: V
authors: Budnik
authors: Pamela K
authors: PK
authors: Geyer
authors: Lori L
authors: LL
authors: Wallrath
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D004440:Ecdysone / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000503:physiopathology*; D015398:Signal Transduction
chemical_list: D034904:Lamin Type A; C440308:lamin C; D004440:Ecdysone