Unique and shared functions of nuclear lamina LEM domain proteins in Drosophila.
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.
Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242.
Lacy J
LJ
Barton
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208.
Shameika R
SR
Wilmington
Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242.
Melinda J
MJ
Martin
Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242.
Hannah M
HM
Skopec
Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242.
Kaylee E
KE
Lovander
Department of Biology, Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Belinda S
BS
Pinto
Department of Biochemistry, University of Iowa, College of Medicine, Iowa City, Iowa 52242 pamela-geyer@uiowa.edu.
Pamela K
PK
Geyer
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D034881:Nuclear Lamina / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010053:Ovary / Q000196:embryology; D010641:Phenotype; D017434:Protein Structure, Tertiary; D014921:Wings, Animal / Q000196:embryology
D029721:Drosophila Proteins; C509056:MAN1 protein, Drosophila; D008565:Membrane Proteins; D009687:Nuclear Proteins; C063595:Ote protein, Drosophila; C492787:bocks protein, Drosophila
Drosophila; LEM domain; germline stem cells; laminopathies; nuclear lamina