title: The minor regulated pathway, a rapid component of salivary secretion, may provide docking/fusion sites for granule exocytosis at the apical surface of acinar cells.
abstract: Recently, we reported that the minor regulated and constitutive-like pathways are the main source of resting secretion by parotid acinar cells. Using tissue lobules biosynthetically labeled with [(35)S]amino acids, we now show that discharge of the minor regulated pathway precedes granule exocytosis stimulated by isoproterenol (> or =1 microM) or carbachol (2 microM). Stimulation of the minor regulated pathway by 40 nM carbachol as well as altering its trafficking, either by adding brefeldin A or by incubating in K(+)-free medium, cause potentiation of amylase secretion stimulated by isoproterenol, suggesting that the minor regulated pathway contributes to the mechanism of potentiation. Both exocytosis of the minor regulated pathway and the potentiation-inducing treatments induce relocation of immunostained subapical puncta of the SNARE protein syntaxin 3 into the apical plasma membrane. Rab11 and possibly VAMP2 may be concentrated in the same relocating foci. These results suggest that the minor regulated pathway and granule exocytosis are functionally linked and that the minor regulated pathway has a second role beyond contributing to resting secretion - providing surface docking/fusion sites for granule exocytosis. In the current model of salivary protein export, discharge of the minor regulated pathway by either beta-adrenergic or cholinergic stimulation is an obligatory first step. Ensuing granule exocytosis is controlled mainly by beta-adrenergic stimulation whereas cholinergic stimulation mainly regulates the number of surface sites where release occurs.
authors.affiliation: Department of Cell Biology, University of Virginia Health System, School of Medicine, Charlottesville 22908-0732, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Castle
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Huang
authors.forename: J David
authors.initials: JD
authors.lastname: Castle
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D010306:Parotid Gland / Q000166:cytology / Q000378:metabolism*; D011191:Potassium Deficiency / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D000318:Adrenergic beta-Agonists; D000596:Amino Acids; D020126:Brefeldin A; D018679:Cholinergic Agonists; D007545:Isoproterenol; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D012471:Salivary Proteins and Peptides; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins