It is proposed to characterize the genes and gene products required for developmentally regulated nuclear migrations in photoreceptors of the Drosophila compound eye. Nuclear migration is of universal importance in animal development. For example, the human brain disorder, Lissencephaly, is the result of neural nuclei failing to migrate appropriately during brain development. Moreover, the Drosophila homolog of the human Lissencephaly gene, Lis1, is essential for photoreceptor nuclear migrations in Drosophila. Thus, the genes and proteins that will be identified and studied are directly relevant to human development and disease. Nuclear migration is an important phenomenon to understand also because of its relationship to other critical processes in eukaryotic development. Many of the proteins important for nuclear migration are also required for the transport of other organelles, establishment of cell polarity, and morphogen localization within the cell. There are four specific goals of the research proposed. The first is a structure/function analysis of Klarsicht, a protein required for photoreceptor nuclear migration. Transgenic flies expressing partial Klarsicht proteins will be used to correlate subcellular localization, protein binding, and organelle migration functions with protein structure.
The second aim i s to clone and characterize the egk1 gene, which like klarsicht, is essential for photoreceptor nuclear migration. Thirdly, antibodies to a variety of proteins will be used to order four nuclear migration genes, klarsicht, egk1, BicD and DLis-1, into a pathway. In addition, the possibility of physical interactions between Klarsicht and Egk1 proteins will be explored using in vivo and in vitro assays. Finally, a variety of different genetic screening approaches will be used to identify additional genes in the klarsicht/egk1 pathway.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY013958-01
Application #
6456916
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Hunter, Chyren
Project Start
2002-04-01
Project End
2006-02-28
Budget Start
2002-04-01
Budget End
2003-02-28
Support Year
1
Fiscal Year
2002
Total Cost
$225,000
Indirect Cost
Name
University of Texas Austin
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78712
Kracklauer, Martin P; Wiora, Heather M; Deery, William J et al. (2010) The Drosophila SUN protein Spag4 cooperates with the coiled-coil protein Yuri Gagarin to maintain association of the basal body and spermatid nucleus. J Cell Sci 123:2763-72
Xie, Xuanhua; Fischer, Janice A (2008) On the roles of the Drosophila KASH domain proteins Msp-300 and Klarsicht. Fly (Austin) 2:74-81
Kracklauer, Martin P; Banks, Susan M L; Xie, Xuanhua et al. (2007) Drosophila klaroid encodes a SUN domain protein required for Klarsicht localization to the nuclear envelope and nuclear migration in the eye. Fly (Austin) 1:75-85
Starr, Daniel A; Fischer, Janice A (2005) KASH 'n Karry: the KASH domain family of cargo-specific cytoskeletal adaptor proteins. Bioessays 27:1136-46
Patterson, Kristin; Molofsky, Ari B; Robinson, Christina et al. (2004) The functions of Klarsicht and nuclear lamin in developmentally regulated nuclear migrations of photoreceptor cells in the Drosophila eye. Mol Biol Cell 15:600-10
Fischer, Janice A; Acosta, Shelley; Kenny, Andrew et al. (2004) Drosophila klarsicht has distinct subcellular localization domains for nuclear envelope and microtubule localization in the eye. Genetics 168:1385-93