Associate Provost for Research Boston University Medical Campus
NEI - National Eye Institute	Research Resources

Abstract

Abstract: DESCRIPTION (provided by applicant): 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.

Thesaurus Terms:
biological signal transduction, cell biology, gene expression, photoconduction, receptor
gene mutation, protein protein interaction, transcription factor
Drosophilidae, confocal scanning microscopy, electron microscopy, genetic screening, immunocytochemistry, mutant, southern blotting

Institution:	BOSTON UNIVERSITY
	881 COMMONWEALTH AVENUE
	BOSTON, MA 02215
Fiscal Year:	2006
Department:	BIOLOGY
Project Start:	01-APR-2003
Project End:	31-MAR-2007
ICD:	NATIONAL EYE INSTITUTE
IRG:	ZRG1