The long-term goal of this research is to determine the mechanisms for sorting and storage of regulated secretory proteins in salivary glands. The answer to this question is important for our understanding of the regulation of protein secretion from salivary glands and, hence, the composition of saliva. Significant progress towards this goal was made in the first grant period. It was shown that calcium- and pH-mediated aggregation do not contribute significantly to the storage of secretory proteins in parotid secretory granules, suggesting that sorting in this gland differs from that of other endocrine and exocrine glands. Indeed, it was demonstrated that sulfated proteoglycans are necessary for efficient storage of secretory proteins in secretory granules of rat parotid acinar cells. The sulfated proteoglycan appears to buffer the internal pH of secretory granules. These results led to the hypothesis that sulfated proteoglycans act as buffering agents that regulate protein sorting and storage in parotid acinar cells.
Specific Aim 1 will test if sulfated proteoglycans act as buffering agents in parotid secretory granules.
Aim 2 will test if expression and) post-translational modification of the proteoglycan core proteins regulates the sorting and storage of other) parotid secretory proteins.
These Aims will employ isoproterenol treatment to overexpress acidic and basic PRPs in rat parotid glands combined with in vitro tissue culture approaches. As an alternative, we will use transgenic mice that overexpress PRPs in salivary glands.
In Aim 3, it will be tested if sulfated proteoglycans play a role in protein or membrane binding of PSP.
Specific Aim 4 will test if sulfated proteoglycans or other acidic proteins are involved in sorting and storage of secretory proteins in the submandibular gland, a current target for gene therapy protocols. The proposed research will use cell biological and molecular methods in salivary cells and protein expression experiments in intact animals. The results of this research will provide insight into the unique sorting mechanisms that function in salivary glands. This will lead to a better understanding of the formation of saliva and provide the basis for efficient delivery of therapeutic proteins from salivary glands.
|Gorr, Sven-Ulrik (2012) Antimicrobial peptides in periodontal innate defense. Front Oral Biol 15:84-98|
|Gorr, Sven-Ulrik; Abdolhosseini, Mahsa (2011) Antimicrobial peptides and periodontal disease. J Clin Periodontol 38 Suppl 11:126-41|
|Venkatesh, S G; Goyal, D; Carenbauer, A L et al. (2011) Parotid secretory protein binds phosphatidylinositol (3,4) bisphosphate. J Dent Res 90:1085-90|
|Gorr, Sven-Ulrik; Abdolhosseini, Mahsa; Shelar, Anuradha et al. (2011) Dual host-defence functions of SPLUNC2/PSP and synthetic peptides derived from the protein. Biochem Soc Trans 39:1028-32|
|Gorr, Sven-Ulrik (2009) Antimicrobial peptides of the oral cavity. Periodontol 2000 51:152-80|
|Fasciotto, Brigitte H; Kuhn, Ulrike; Cohn, David V et al. (2008) Secretory cargo composition affects polarized secretion in MDCK epithelial cells. Mol Cell Biochem 310:67-75|
|Venkatesh, Srirangapatnam G; Tan, Jinlian; Gorr, Sven-Ulrik et al. (2007) Isoproterenol increases sorting of parotid gland cargo proteins to the basolateral pathway. Am J Physiol Cell Physiol 293:C558-65|
|Shiba, Hideki; Venkatesh, S G; Gorr, Sven-Ulrik et al. (2005) Parotid secretory protein is expressed and inducible in human gingival keratinocytes. J Periodontal Res 40:153-7|
|Geetha, C; Venkatesh, S G; Bingle, L et al. (2005) Design and validation of anti-inflammatory peptides from human parotid secretory protein. J Dent Res 84:149-53|
|Gorr, S-U; Venkatesh, S G; Darling, D S (2005) Parotid secretory granules: crossroads of secretory pathways and protein storage. J Dent Res 84:500-9|
Showing the most recent 10 out of 18 publications