Heparan sulfate is a type of glycosaminoglycan (GAG) characterized by alternating uronic acid and D-glucosamine units (Esko and Lindahl, 2001). Heparan sulfate can be found on a number of cell types in a wide range of species from early metazoans to human cells. The chains are assembled while attached to a core protein, and the composite structure is called a proteoglycan. Heparan sulfate proteoglycans can be membrane-intercalated or GPI anchored, secreted, or stored in granules along with other secretory products (Bernfield et al., 1999). Proteoglycans function in a wide array of cellular activities including signaling, cell adhesion, and migration. T cells produce heparan sulfate(Wilson and Rider, 1991) and it is likely that heparan sulfate plays a critical role in their development and activation. This proposal contains a series of experiments that will examine the structure, assembly, and function of heparan sulfate proteoglycans in T cells. One set of experiments examines the composition of heparan sulfate proteoglycans in different T-cell subsets.
A second aim focuses on the effect of inactivating a key heparan sulfate biosynthetic enzyme, GIcNAc N-deacetylase/N-sulfotransferase (NDST) on T cell development and activation. The long range goals of this study are to better understand the function of heparan sulfate in cell biology, which may provide novel targets for pharmacologic intervention in T cell mediated immunity. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI058916-04
Application #
7213318
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Hernandez, Milton J
Project Start
2004-04-01
Project End
2008-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
4
Fiscal Year
2007
Total Cost
$30,064
Indirect Cost
Name
University of California San Diego
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Bush, Kevin T; Crawford, Brett E; Garner, Omai B et al. (2012) N-sulfation of heparan sulfate regulates early branching events in the developing mammary gland. J Biol Chem 287:42064-70
Garner, Omai B; Bush, Kevin T; Nigam, Kabir B et al. (2011) Stage-dependent regulation of mammary ductal branching by heparan sulfate and HGF-cMet signaling. Dev Biol 355:394-403
Crawford, Brett E; Garner, Omai B; Bishop, Joseph R et al. (2010) Loss of the heparan sulfate sulfotransferase, Ndst1, in mammary epithelial cells selectively blocks lobuloalveolar development in mice. PLoS One 5:e10691
Garner, Omai B; Yamaguchi, Yu; Esko, Jeffrey D et al. (2008) Small changes in lymphocyte development and activation in mice through tissue-specific alteration of heparan sulphate. Immunology 125:420-9