The goal of this research is to test the hypothesis that sodium channel beta subunits interact with extracellular matrix molecules, membrane receptors, and intracellular signaling proteins to modulate cell adhesion. Specifically, the first aim will identify the domains of tenascin-R responsible for binding to the Nay 1.2 and the beta-1 subunit of the sodium channel using gel overlay and coimmunoprecipitation assays.
The second aim examines the ability of beta-1 to interact with the FGF receptor during ligand binding and homophillic events to cause downstream signaling.
The final aim examines whether potential SH2 and SHPTP-2 binding motifs within the intracellular domain of beta-1 are able to recruit non-receptor tyrosine kinases such as lck, fyn or crk. Since mutations in cell adhesion molecules, including sodium channel beta-1 subunits, are linked to several inherited diseases; a basic understanding of the biology of cell adhesion associated with sodium channel beta-1 subunits and like molecules may lead to therapeutic advances for these debilitating diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31NS043062-02
Application #
6622434
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Stewart, Randall
Project Start
2002-02-01
Project End
2005-01-31
Budget Start
2003-02-01
Budget End
2004-01-31
Support Year
2
Fiscal Year
2003
Total Cost
$30,398
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pharmacology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Brackenbury, William J; Davis, Tigwa H; Chen, Chunling et al. (2008) Voltage-gated Na+ channel beta1 subunit-mediated neurite outgrowth requires Fyn kinase and contributes to postnatal CNS development in vivo. J Neurosci 28:3246-56
Davis, Tigwa H; Chen, Chunling; Isom, Lori L (2004) Sodium channel beta1 subunits promote neurite outgrowth in cerebellar granule neurons. J Biol Chem 279:51424-32