Journal article
A comparative study of Drosophila and human A-type lamins
PloS one, Vol.4(10), pp.e7564-e7564
10/26/2009
DOI: 10.1371/journal.pone.0007564
PMCID: PMC2762312
PMID: 19855837
Abstract
Nuclear intermediate filament proteins, called lamins, form a meshwork that lines the inner surface of the nuclear envelope. Lamins contain three domains: an N-terminal head, a central rod and a C-terminal tail domain possessing an Ig-fold structural motif. Lamins are classified as either A- or B-type based on structure and expression pattern. The Drosophila genome possesses two genes encoding lamins, Lamin C and lamin Dm(0), which have been designated A- and B-type, respectively, based on their expression profile and structural features. In humans, mutations in the gene encoding A-type lamins are associated with a spectrum of predominantly tissue-specific diseases known as laminopathies. Linking the disease phenotypes to cellular functions of lamins has been a major challenge. Drosophila is being used as a model system to identify the roles of lamins in development. Towards this end, we performed a comparative study of Drosophila and human A-type lamins. Analysis of transgenic flies showed that human lamins localize predictably within the Drosophila nucleus. Consistent with this finding, yeast two-hybrid data demonstrated conservation of partner-protein interactions. Drosophila lacking A-type lamin show nuclear envelope defects similar to those observed with human laminopathies. Expression of mutant forms of the A-type Drosophila lamin modeled after human disease-causing amino acid substitutions revealed an essential role for the N-terminal head and the Ig-fold in larval muscle tissue. This tissue-restricted sensitivity suggests a conserved role for lamins in muscle biology. In conclusion, we show that (1) localization of A-type lamins and protein-partner interactions are conserved between Drosophila and humans, (2) loss of the Drosophila A-type lamin causes nuclear defects and (3) muscle tissue is sensitive to the expression of mutant forms of A-type lamin modeled after those causing disease in humans. These studies provide new insights on the role of lamins in nuclear biology and support Drosophila as a model for studies of human laminopathies involving muscle dysfunction.
Details
- Title: Subtitle
- A comparative study of Drosophila and human A-type lamins
- Creators
- Sandra R Schulze - Department of Biology, Western Washington University, Bellingham, Washington, United States of AmericaBeatrice Curio-PennySean SpeeseGeorge DialynasDiane E CrydermanCaitrin W McDonoughDemet NalbantMelissa PetersenVivian BudnikPamela K GeyerLori L Wallrath
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.4(10), pp.e7564-e7564
- DOI
- 10.1371/journal.pone.0007564
- PMID
- 19855837
- PMCID
- PMC2762312
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- R01 MH070000 / NIMH NIH HHS
- Language
- English
- Date published
- 10/26/2009
- Academic Unit
- Stead Family Department of Pediatrics; Obstetrics and Gynecology; Biochemistry and Molecular Biology; University College Courses
- Record Identifier
- 9984024415002771
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