Cell Biology of Salivary Protein Secretion - PowerPoint by W183BrAx

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									Cell Biology of Salivary Protein

  Biology of salivary glands (BMS 513)
        Nisha D’Silva DDS, PhD
       Wednesday, May 16, 2001
          9 - 10 am, Rm. G322

1. Review anatomy and Histology
2. Secretory pathways
3. Signaling mechanism in regulated
4. Brief discussion about drugs and saliva.
Major salivary glands
Histology of an acinar unit
Histology of major salivary
            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

 Too large to cross the cell membrane
 Must be synthesized and stored within a
  membrane-bound vesicle and released by
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
 Secretory proteins are concentrated and stored in
  secretory vesicles
 Mature vesicles are transported to apical membrane
 Secretory stimuli result in vesicle fusion with plasma
 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
 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
 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)

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