Journal article
Unique and shared functions of nuclear lamina LEM domain proteins in Drosophila
Genetics (Austin), Vol.197(2), pp.653-665
06/2014
DOI: 10.1534/genetics.114.162941
PMCID: PMC4063922
PMID: 24700158
Abstract
The nuclear lamina is an extensive protein network that contributes to nuclear structure and function. LEM domain (LAP2, emerin, MAN1 domain, LEM-D) proteins are components of the nuclear lamina, identified by a shared ∼45-amino-acid motif that binds Barrier-to-autointegration factor (BAF), a chromatin-interacting protein. Drosophila melanogaster has three nuclear lamina LEM-D proteins, named Otefin (Ote), Bocksbeutel (Bocks), and dMAN1. Although these LEM-D proteins are globally expressed, loss of either Ote or dMAN1 causes tissue-specific defects in adult flies that differ from each other. The reason for such distinct tissue-restricted defects is unknown. Here, we generated null alleles of bocks, finding that loss of Bocks causes no overt adult phenotypes. Next, we defined phenotypes associated with lem-d double mutants. Although the absence of individual LEM-D proteins does not affect viability, loss of any two proteins causes lethality. Mutant phenotypes displayed by lem-d double mutants differ from baf mutants, suggesting that BAF function is retained in animals with a single nuclear lamina LEM-D protein. Interestingly, lem-d double mutants displayed distinct developmental and cellular mutant phenotypes, suggesting that Drosophila LEM-D proteins have developmental functions that are differentially shared with other LEM-D family members. This conclusion is supported by studies showing that ectopically produced LEM-D proteins have distinct capacities to rescue the tissue-specific phenotypes found in single lem-d mutants. Our findings predict that cell-specific mutant phenotypes caused by loss of LEM-D proteins reflect both the constellation of LEM-D proteins within the nuclear lamina and the capacity of functional compensation of the remaining LEM-D proteins.
Details
- Title: Subtitle
- Unique and shared functions of nuclear lamina LEM domain proteins in Drosophila
- Creators
- Lacy J Barton - Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242Shameika R Wilmington - Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208Melinda J Martin - Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242Hannah M Skopec - Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242Kaylee E Lovander - Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242Belinda S Pinto - Department of Biology, Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142Pamela K Geyer - Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242 pamela-geyer@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Genetics (Austin), Vol.197(2), pp.653-665
- Publisher
- United States
- DOI
- 10.1534/genetics.114.162941
- PMID
- 24700158
- PMCID
- PMC4063922
- ISSN
- 0016-6731
- eISSN
- 1943-2631
- Grant note
- GM087341 / NIGMS NIH HHS R01 GM087341 / NIGMS NIH HHS S10 RR025439 / NCRR NIH HHS P30 CA086862 / NCI NIH HHS S10RR025439-01 / NCRR NIH HHS
- Language
- English
- Date published
- 06/2014
- Academic Unit
- Obstetrics and Gynecology; Biochemistry and Molecular Biology
- Record Identifier
- 9984025263302771
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