Growing neurons must recognize and follow specific pathways to their synaptic targets by sensing guidance cues that regulate cell motility. In Drosophila, the Drl receptor is expressed by a subset of neurons and is required for proper axon pathfinding. Drl is a member of the Ryk family of atypical receptor tyrosine kinases (RTKs), which are catalytically inactive receptors for Wnt ligands. Wnt ligands, which typically function in signaling pathways distinct from RTKs, are involved in multiple disease processes such as cancer cell nvasiveness and metastasis. The human Drl ortholog, Ryk, has also been implicated in numerous cancers. Yet, little is known about the signaling events initiated by Ryk family receptors in response to Wnts. The broader goal of this proposal is to identify and characterize the signaling pathways employed by Drl and Wnt proteins to regulate cell motility. Drl signaling activity will be elucidated using proteomic, cell-biological, and genetic approaches to 1) Analyze the Drl cytoplasmic domain for functional regions, 2) Investigate the role Drl ntramembrane proteolysis and the function of the released Drl cytoplasmic domain, 3) Identify Drl binding proteins, and 4) Characterize Drl-binding proteins and candidate Drl signaling effectors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS053259-02
Application #
7217560
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Riddle, Robert D
Project Start
2005-09-30
Project End
2008-09-29
Budget Start
2006-09-30
Budget End
2007-09-29
Support Year
2
Fiscal Year
2006
Total Cost
$48,796
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Read, Renee D; Cavenee, Webster K; Furnari, Frank B et al. (2009) A drosophila model for EGFR-Ras and PI3K-dependent human glioma. PLoS Genet 5:e1000374