Department of Neurobiology; Budnik Lab
Animals; Animals, Genetically Modified; Cell Nucleus; Drosophila melanogaster; Gene Expression Regulation; Humans; Lamin Type A; Muscles; Mutation; Nuclear Envelope; Tissue Distribution; Two-Hybrid System Techniques
Neuroscience and Neurobiology
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.
Rights and Permissions
Copyright: © 2009 Schulze et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Schulze SR, Curio-Penny B, Speese S, Dialynas G, Cryderman DE, et al. (2009) A Comparative Study of Drosophila and Human A-Type Lamins. PLoS ONE 4(10): e7564. doi:10.1371/journal.pone.0007564. Link to article on publisher's site
Schulze SR, Curio-Penny B, Speese SD, 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. Neurobiology Publications. https://doi.org/10.1371/journal.pone.0007564. Retrieved from https://escholarship.umassmed.edu/neurobiology_pp/25