A comparative study of Drosophila and human A-type lamins

Sandra R. Schulze, Beatrice Curio-Penny, Sean Speese, George Dialynas, Diane E. Cryderman, Caitrin W. McDonough, Demet Nalbant, Melissa Petersen, Vivian Budnik, Pamela K. Geyer, Lori L. Wallrath

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 Dm0, 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.

Original languageEnglish (US)
Article numbere7564
JournalPLoS One
Volume4
Issue number10
DOIs
StatePublished - Oct 26 2009
Externally publishedYes

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Lamins
Lamin Type A
Drosophila
Muscle
Tissue
Muscles
nuclear membrane
Nuclear Envelope
Gene encoding
muscle tissues
human diseases
intermediate filament proteins
Head
Biological Sciences
muscles
mutants
Intermediate Filament Proteins
nuclear proteins
amino acid substitution
Defects

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Schulze, S. R., Curio-Penny, B., Speese, S., Dialynas, G., Cryderman, D. E., McDonough, C. W., ... Wallrath, L. L. (2009). A comparative study of Drosophila and human A-type lamins. PLoS One, 4(10), [e7564]. https://doi.org/10.1371/journal.pone.0007564

A comparative study of Drosophila and human A-type lamins. / Schulze, Sandra R.; Curio-Penny, Beatrice; Speese, Sean; Dialynas, George; Cryderman, Diane E.; McDonough, Caitrin W.; Nalbant, Demet; Petersen, Melissa; Budnik, Vivian; Geyer, Pamela K.; Wallrath, Lori L.

In: PLoS One, Vol. 4, No. 10, e7564, 26.10.2009.

Research output: Contribution to journalArticle

Schulze, SR, Curio-Penny, B, Speese, S, Dialynas, G, Cryderman, DE, McDonough, CW, Nalbant, D, Petersen, M, Budnik, V, Geyer, PK & Wallrath, LL 2009, 'A comparative study of Drosophila and human A-type lamins', PLoS One, vol. 4, no. 10, e7564. https://doi.org/10.1371/journal.pone.0007564
Schulze SR, Curio-Penny B, Speese S, Dialynas G, Cryderman DE, McDonough CW et al. A comparative study of Drosophila and human A-type lamins. PLoS One. 2009 Oct 26;4(10). e7564. https://doi.org/10.1371/journal.pone.0007564
Schulze, Sandra R. ; Curio-Penny, Beatrice ; Speese, Sean ; Dialynas, George ; Cryderman, Diane E. ; McDonough, Caitrin W. ; Nalbant, Demet ; Petersen, Melissa ; Budnik, Vivian ; Geyer, Pamela K. ; Wallrath, Lori L. / A comparative study of Drosophila and human A-type lamins. In: PLoS One. 2009 ; Vol. 4, No. 10.
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