Author:
Venkatesh Srirangapatnam G.,Tan Jinlian,Gorr Sven-Ulrik,Darling Douglas S.
Abstract
Exocrine cells have an essential function of sorting secreted proteins into the correct secretory pathway. A clear understanding of sorting in salivary glands would contribute to the correct targeting of therapeutic transgenes. The present work investigated whether there is a change in the relative proportions of basic proline-rich protein (PRP) and acidic PRPs in secretory granules in response to chronic isoproterenol treatment, and whether this alters the sorting of endogenous cargo proteins. Immunoblot analysis of secretory granules from rat parotids found a large increase of basic PRP over acidic PRPs in response to chronic isoproterenol treatment. Pulse chase experiments demonstrated that isoproterenol also decreased regulated secretion of newly synthesized secretory proteins, including PRPs, amylase and parotid secretory protein. This decreased efficiency of the apical regulated pathway may be mediated by alkalization of the secretory granules since it was reversed by treatment with mild acid. We also investigated changes in secretion through the basolateral (endocrine) pathways. A significant increase in parotid secretory protein and salivary amylase was detected in sera of isoproterenol-treated animals, suggesting increased routing of the regulated secretory proteins to the basolateral pathway. These studies demonstrate that shifts of endogenous proteins can modulate regulated secretion and sorting of cargo proteins.
Publisher
American Physiological Society
Reference54 articles.
1. Ann DK, Clements S, Johnstone EM, Carlson DM.Induction of tissue-specific proline-rich protein multigene families in rat and mouse parotid glands by isoproterenol. Unusual strain differences of proline-rich protein mRNAs.J Biol Chem262: 899–904, 1987.
2. Sorting and storage during secretory granule biogenesis: looking backward and looking forward
3. Isolated secretion granules from parotid glands of chronically stimulated rats possess an alkaline internal pH and inward-directed H+ pump activity.
4. Arvan P, Kuliawat R, Prabakaran D, Zavacki AM, Elahi D, Wang S, Pilkey D.Protein discharge from immature secretory granules displays both regulated and constitutive characteristics.J Biol Chem266: 14171–14174, 1991.
5. Polarized Secretion of Transgene Products from Salivary Glands in Vivo
Cited by
9 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献