An area of intense interest in neurobiology is to understand the molecular basis for axon guidance and targeting. Genetic, biochemical and cell biological approaches have lent considerable insight into the relevant underpinnings to these phenomena. The Poo and Tessier-Lavigne lab have provided insight into the molecular details of netrin-1 (N1) and rMAG induced chemotropism in spinal neurons. Recently, they reported that N1 and rMAG mediated attraction or repulsion, respectively, required both the cAMP and Ca2+ signaling pathways. However, the precise details of how cAMP and Ca2+ promote attractive or repulsive responses in growth cones are unknown. This proposal focuses on the downstream events after DCC or MAG receptor occupancy during neurite reorientation toward gradients of N1 or rMAG. It is possible that gradients of cAMP and Ca2+ are established in the cytoplasm in response to external gradients of N1 or rMAG and asymmetrically modify the cytoskeleton to reorient the growth cone toward or away from a guidance cue source. This study will examine the causal relationship between the AMP and Ca2+ pathways with respect to cytoskeletal rearrangement. Furthermore, it will determine if intracellular gradients of PI3 kinase activity are involved. This study could provide insights into the development of better approaches for treating spinal cord or peripheral nerve damage after injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS011126-04
Application #
6625547
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Mamounas, Laura
Project Start
2001-12-01
Project End
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
4
Fiscal Year
2003
Total Cost
$46,420
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704