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. ? ?
| 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 |
