title: Elevated prolactin redirects secretory vesicle traffic in rabbit lacrimal acinar cells.
abstract: During pregnancy, lymphocytes infiltrating the rabbit lacrimal gland disperse to the interacinar space from their normal focal concentrations, basal fluid secretion decreases, pilocarpine-induced fluid secretion increases, and stimulated fluid protein concentration decreases. Ductal epithelial cell prolactin (PRL) content increases and redistributes from the apical to the basal-lateral cytoplasm. A replication-incompetent adenovirus vector for rabbit PRL (AdPRL) was used to test the hypothesis that increased intracrine/autocrine PRL signaling alters secretory protein traffic in an ex vivo lacrimal acinar cell model. AdPRL had no discernable influence on microtubules or actin microfilaments or their responses to carbachol (CCh). Endogenous and transduced PRLs exhibited similar, nonpolarized, punctate distributions. Cells secreted PRL consititutively and at increased rates in response to CCh. In contrast, constitutive secretion of beta-hexosaminidase was negligible, suggesting that the constitutive pathway for PRL is relatively inaccessible to typical secretory proteins. AdPRL had no significant effect on total secretion of beta-hexosaminidase or syncollin-green fluorescent protein (GFP), a chimeric secretory protein construct. However, it reversed the polarized distributions of vesicles containing rab3D and syncollin-GFP. Live-cell imaging indicated that AdPRL redirected CCh-dependent syncollin-GFP exocytosis from the apical plasma membrane to the basal-lateral membrane. Elevated concentrations of exogenous rabbit PRL in the ambient medium elicited similar changes. These observations suggest that elevated PRL, as occurs in the physiological hyperprolactinemia of pregnancy, induces lacrimal epithelial cells to express a mixed exocrine/endocrine phenotype that secretes fluid to the acinus-duct lumen but secretes proteins to the underlying tissue space. This phenotype may contribute to the pregnancy-associated immunoarchitecture.
authors.affiliation: Department of Physiology & Biophysics, Keck School of Medicine, University of Southern California, 1333 San Pablo St., MMR 626, Los Angeles, CA 90033, USA.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Chiu
authors.forename: Tamako
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ameae M
authors.initials: AM
authors.lastname: Walker
authors.forename: Barbara
authors.initials: B
authors.lastname: Petridou
authors.forename: Melvin D
authors.initials: MD
authors.lastname: Trousdale
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Hamm-Alvarez
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schechter
authors.forename: Austin K
authors.initials: AK
authors.lastname: Mircheff
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D002217:Carbachol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D007425:Intracellular Membranes / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics; D011388:Prolactin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D014161:Transduction, Genetic; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C107454:Sycn protein, rat; D049452:Green Fluorescent Proteins; D002217:Carbachol; D011388:Prolactin; D001619:beta-N-Acetylhexosaminidases; D020692:rab3 GTP-Binding Proteins