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: George Dialynas, Sean Speese, Vivian Budnik, Pamela K Geyer, Lori L Wallrath
• Journal: Development (Cambridge, England) (Development) Vol. 137 Issue 18 Pg. 3067-77 (Sep 2010) ISSN: 1477-9129 [Electronic] England
• PMID: 20702563 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Lamin Type A
• lamin C
• Ecdysone

Topics

• Animals
• Cell Nucleus (metabolism)
• Drosophila melanogaster (anatomy & histology, genetics, physiology)
• Ecdysone (metabolism)
• Gene Expression Regulation, Developmental
• Lamin Type A (genetics, metabolism)
• Muscles (physiopathology)
• Signal Transduction