Journal article
Tissue-Specific Defects Are Caused by Loss of the Drosophila MAN1 LEM Domain Protein
Genetics (Austin), Vol.180(1), pp.133-145
09/2008
DOI: 10.1534/genetics.108.091371
PMCID: PMC2535669
PMID: 18723885
Abstract
The nuclear lamina represents a protein network required for nuclear structure and function. One family of lamina proteins is defined by an ∼40-aa
L
AP2,
E
merin, and
M
AN1 (LEM) domain (LEM-D) that binds the nonspecific DNA-binding protein, barrier-to-autointegration factor (BAF). Through interactions with BAF, LEM-D proteins serve as a bridge between chromosomes and the nuclear envelope. Mutations in genes encoding LEM-D proteins cause human laminopathies that are associated with tissue-restricted pathologies. Drosophila has five genes that encode proteins with LEM homology. Using yeast two-hybrid analyses, we demonstrate that four encode proteins that bind Drosophila (d)BAF. In addition to dBAF, dMAN1 associates with lamins, the LEM-D protein Bocksbeutel, and the receptor-regulated Smads, demonstrating parallel protein interactions with vertebrate homologs.
P
-element mobilization was used to generate null
dMAN1
alleles. These mutants showed decreased viability, with surviving adults displaying male sterility, decreased female fertility, wing patterning and positioning defects, flightlessness, and locomotion difficulties that became more severe with age. Increased phospho-Smad staining in
dMAN1
mutant wing discs is consistent with a role in transforming growth factor (TGF)-β/bone morphogenic protein (BMP) signaling. The tissue-specific, age-enhanced
dMAN1
mutant phenotypes are reminiscent of human laminopathies, suggesting that studies in Drosophila will provide insights into lamina dysfunction associated with disease.
Details
- Title: Subtitle
- Tissue-Specific Defects Are Caused by Loss of the Drosophila MAN1 LEM Domain Protein
- Creators
- Belinda S Pinto - Molecular and Cellular Biology Program andShameika R Wilmington - Molecular and Cellular Biology Program andEmma E. L Hornick - Molecular and Cellular Biology Program andLori L Wallrath - Molecular and Cellular Biology Program andPamela K Geyer - Molecular and Cellular Biology Program and
- Resource Type
- Journal article
- Publication Details
- Genetics (Austin), Vol.180(1), pp.133-145
- Publisher
- Genetics Society of America
- DOI
- 10.1534/genetics.108.091371
- PMID
- 18723885
- PMCID
- PMC2535669
- ISSN
- 0016-6731
- eISSN
- 1943-2631
- Language
- English
- Date published
- 09/2008
- Academic Unit
- Microbiology and Immunology; Obstetrics and Gynecology; Biochemistry and Molecular Biology; University College Courses
- Record Identifier
- 9984024559202771
Metrics
21 Record Views