Post on 04-Jan-2016
Cell Biology of Salivary Protein Secretion
Biology of salivary glands (BMS 513)Nisha D’Silva DDS, PhD
Wednesday, May 16, 20019 - 10 am, Rm. G322
Overview
1. Review anatomy and Histology
2. Secretory pathways
3. Signaling mechanism in regulated secretion.
4. Brief discussion about drugs and saliva.
Major salivary glands
Histology of an acinar unit
Histology of major salivary glands
Macromolecule secretion Polypeptides and proteins are synthesized and secreted
by the salivary acinar cells Sublingual saliva -- very thick and viscous
– produced by mucous acinar cells Parotid saliva -- thin and watery
– produced by serous acinar cells– mainly salivary amylase and proline-rich polypeptides
Submandibular saliva -- intermediate consistency– a mix of serous and mucous acini
Regardless of the type of protein
Too large to cross the cell membrane Must be synthesized and stored within a
membrane-bound vesicle and released by exocytosis
Protein synthesis and secretory pathways
Protein synthesis and secretion Genes transcribed in nucleus to make mRNA Message is transferred to ribosomes in cytoplasm Secretory proteins begin with signal sequence which
targets developing peptide to endoplasmic reticulum At ER, peptide is N-glycosylated and folded into
correct 3D structure Small membrane vesicles carry proteins from ER
through several layers of the golgi apparatus for additional processing and packaging for export
Protein synthesis and secretion (cont’d)
Proteins move by default onwards from the ER Specific retention sequences segregate non-secreted
proteins Secretory proteins are concentrated and stored in
secretory vesicles Mature vesicles are transported to apical membrane Secretory stimuli result in vesicle fusion with plasma
membrane Contents of vesicles are discharged outside of cell
Secretory pathways 1. Constitutive - occurs continuously 2. Regulated 3. Paragranular - small vesicles
break-off from SGs that undergo regulated secretion and are released
Constitutive exocytosis
Differs from regulated exocytosis Proteins not concentrated into secretory vesicles
awaiting exocytotic stimulus Continuous flow of protein in small vesicles to
plasma membrane Regulation occurs at synthesis stage
Regulated secretion in salivary glands
Mechanism of action of G- proteins
Control of protein secretion: second messengers
Each stage of secretion is regulated by phosphorylation of target proteins
Phosphorylation is carried out by a protein kinase such as cyclic adenosine monophosphate (cAMP)-dependent protein kinase (protein kinase A) or PKC
» cAMP stimulates maturation and translocation of secretory vesicles to the apical membrane
» cAMP stimulates exocytosis
Regulated secretion in salivary glands
Four stages of cAMP production
Nordrenaline (NA) binds to -adrenergic receptors G-protein (Gs) associated with the -adrenergic
receptor moves to an active GTP-bound state The Gs-GTP stimulates adenylate cyclase to convert
ATP into cAMP cAMP activates protein kinase A which
phosphorylates target proteins
Regulated secretion in salivary glands
Crosstalk
Fluid and protein secretion occurs by different mechanisms controlled by different nerves
Separation between control of protein and electrolytes breaks down at second messenger level
Interaction between Ca2+ and cAMP-mediated events (cross-talk) allows combination of intracellular signaling pathways into an integrated stimulus-secretion coupling mechanism.
Drugs and secretion
1. Propranolol (Inderal): -blocker
2. Pilocarpine (Salagen): cholinergic agonist
parasympathetic pathway
3. Atropine: (Atropisol, Sal-Tropine)
anti-cholinergic.
Summary