? An important issue in the field of signal transduction is how signaling molecules are organized into different pathways within the same cell. Our goal is to understand how the signal transduction cascade that underlies the phototransduction process is organized, and how individual components interact and participate in normal visual function. The importance of assembling signaling molecules into architecturally defined complexes has emerged as an essential cellular strategy to ensure speed and specificity of signaling. Results in Drosophila photoreceptors as well as in other systems and organisms have further demonstrated that the subcellular localization of these signaling complexes is essential for effective signaling. Mislocalization of signaling components is often the equivalent of their absence, and consequences can be severe. Critical questions that arise then are: how are signaling complexes targeted to the right subcellular domain? How and where are they assembled? How is this assembly regulated? How are they anchored or stabilized in the proper locale? This grant proposal focuses on a molecular-genetic dissection of the assembly and localization of signaling complexes in Drosophila photoreceptors. We will 1) perform a comprehensive genetic screen to isolate mutations affecting the proper localization of signaling complexes in photoreceptors, 2) characterize the mutants genetically, cell biologically, and physiologically, 3) isolate the defective genes, compare the homologous sequence from wild-type flies, identify the nature of the change, and introduce the wild-type gene back into flies and test for rescue of the phenotype, 4) for those genes that warrant further investigation, we will study how the proteins they encode function in assembly and localization processes. Components and strategies used in Drosophila are likely to be conserved in mammals. We expect to identify and characterize key components in the assembly, regulation of assembly, targeting, and anchoring of signaling complexes. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY013751-03S1
Application #
7127826
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mariani, Andrew P
Project Start
2003-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
3
Fiscal Year
2005
Total Cost
$37,022
Indirect Cost
Name
Boston University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Lieu, Minh-Ha; Vallejos, Maximiliano J; Michael, Emily et al. (2012) Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors. PLoS One 7:e31622
Sanxaridis, Parthena D; Tsunoda, Susan (2010) A forward genetic screen in Drosophila melanogaster to identify mutations affecting INAD localization in photoreceptor cells. Fly (Austin) 4:95-103
Acharya, Jairaj K; Dasgupta, Ujjaini; Rawat, Satinder S et al. (2008) Cell-nonautonomous function of ceramidase in photoreceptor homeostasis. Neuron 57:69-79
Sanxaridis, Parthena D; Cronin, Michelle A; Rawat, Satinder S et al. (2007) Light-induced recruitment of INAD-signaling complexes to detergent-resistant lipid rafts in Drosophila photoreceptors. Mol Cell Neurosci 36:36-46
Cronin, Michelle A; Lieu, Minh-Ha; Tsunoda, Susan (2006) Two stages of light-dependent TRPL-channel translocation in Drosophila photoreceptors. J Cell Sci 119:2935-44
Cronin, Michelle A; Diao, Fengqiu; Tsunoda, Susan (2004) Light-dependent subcellular translocation of Gqalpha in Drosophila photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC. J Cell Sci 117:4797-806