title: Ca²⁺-regulated secretory granule exocytosis in pancreatic and parotid acinar cells.
abstract: Protein secretion from acinar cells of the pancreas and parotid glands is controlled by G-protein coupled receptor activation and generation of the cellular messengers Ca(2+), diacylglycerol and cAMP. Secretory granule (SG) exocytosis shares some common characteristics with nerve, neuroendocrine and endocrine cells which are regulated mainly by elevated cell Ca(2+). However, in addition to diverse signaling pathways, acinar cells have large ∼1 μm diameter SGs (∼30 fold larger diameter than synaptic vesicles), respond to stimulation at slower rates (seconds versus milliseconds), demonstrate significant constitutive secretion, and in isolated acini, undergo sequential compound SG-SG exocytosis at the apical membrane. Exocytosis proceeds as an initial rapid phase that peaks and declines over 3 min followed by a prolonged phase that decays to near basal levels over 20-30 min. Studies indicate the early phase is triggered by Ca(2+) and involves the SG proteins VAMP2 (vesicle associated membrane protein2), Ca(2+)-sensing protein synatotagmin 1 (syt1) and the accessory protein complexin 2. The molecular details for regulation of VAMP8-mediated SG exocytosis and the prolonged phase of secretion are still emerging. Here we review the known regulatory molecules that impact the sequential exocytic process of SG tethering, docking, priming and fusion in acinar cells.
authors.affiliation: Department of Nutritional Sciences, Graduate Program in Biochemical and Molecular Nutrition, University of Wisconsin, Madison, WI 53706, United States.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Messenger
authors.affiliation: Department of Nutritional Sciences, Graduate Program in Biochemical and Molecular Nutrition, University of Wisconsin, Madison, WI 53706, United States.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Falkowski
authors.affiliation: Department of Nutritional Sciences, Graduate Program in Biochemical and Molecular Nutrition, University of Wisconsin, Madison, WI 53706, United States. Electronic address: groby@nutrisci.wisc.edu.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Groblewski
mesh_terms: D061354:Acinar Cells / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D005089:Exocytosis; D006801:Humans; D010179:Pancreas / Q000378:metabolism*; D010306:Parotid Gland / Q000378:metabolism*; D050600:SNARE Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D050600:SNARE Proteins; D034501:Telomere-Binding Proteins; D050988:Vesicle-Associated Membrane Protein 2; D000242:Cyclic AMP; D002118:Calcium
keywords: Acinar exocytosis; Ca(2+); Complexin; Docking; Fusion; Membrane trafficking; Pancreatic parotid acinar secretion; SNARE; Secretory granules; Synaptotagmin; Tethering; Zymogen granules; cAMP
references.citation: Arch Biochem Biophys. 2004 Nov 1;431(1):124-8
references.pmid: 15464734
references.citation: PLoS One. 2012;7(5):e37048
references.pmid: 22615885
references.citation: J Biol Chem. 2005 Nov 25;280(47):39175-84
references.pmid: 16186111
references.citation: Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G561-70
references.pmid: 15920016
references.citation: Pflugers Arch. 2002 Aug;444(5):586-96
references.pmid: 12194011
references.citation: Am J Physiol Gastrointest Liver Physiol. 2011 Aug;301(2):G306-16
references.pmid: 21636530
references.citation: J Biol Chem. 2011 Aug 26;286(34):29627-34
references.pmid: 21733851
references.citation: Biochem J. 1998 Feb 15;330 ( Pt 1):329-34
references.pmid: 9461527
references.citation: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13552-7
references.pmid: 21808006
references.citation: Arch Oral Biol. 2009 Apr;54(4):361-8
references.pmid: 19185850
references.citation: Mol Cell Proteomics. 2006 Feb;5(2):306-12
references.pmid: 16278343
references.citation: Traffic. 2008 Sep;9(9):1414-24
references.pmid: 18445120
references.citation: Nat Struct Mol Biol. 2013 Jun;20(6):679-86
references.pmid: 23665582
references.citation: J Biol Chem. 2008 Aug 29;283(35):23884-94
references.pmid: 18577515
references.citation: Am J Physiol. 1997 Sep;273(3 Pt 1):G655-60
references.pmid: 9316469
references.citation: Arch Biochem Biophys. 2004 Feb 15;422(2):175-82
references.pmid: 14759605
references.citation: Nature. 1995 Mar 9;374(6518):173-7
references.pmid: 7877690
references.citation: J Cell Biol. 1995 Feb;128(4):589-98
references.pmid: 7860632
references.citation: Curr Opin Cell Biol. 2010 Aug;22(4):496-505
references.pmid: 20561775
references.citation: Front Endocrinol (Lausanne). 2013 Sep 18;4:124
references.pmid: 24065953
references.citation: Yonsei Med J. 2006 Feb 28;47(1):70-7
references.pmid: 16502487
references.citation: J Cell Biol. 2011 Dec 26;195(7):1159-70
references.pmid: 22184197
references.citation: J Biol Chem. 2004 Sep 3;279(36):37544-50
references.pmid: 15184362
references.citation: PLoS One. 2013 Sep 27;8(9):e76278
references.pmid: 24086721
references.citation: J Cell Sci. 2004 Apr 15;117(Pt 10):1945-53
references.pmid: 15039459
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 May;292(5):G1403-10
references.pmid: 17234888
references.citation: Jpn J Physiol. 1983;33(5):687-98
references.pmid: 6199537
references.citation: J Cell Biol. 1987 Feb;104(2):243-52
references.pmid: 2433293
references.citation: J Cell Biol. 2012 Apr 16;197(2):301-12
references.pmid: 22508512
references.citation: J Autoimmun. 2012 Aug;39(1-2):83-92
references.pmid: 22285554
references.citation: Annu Rev Biochem. 2008;77:615-41
references.pmid: 18275379
references.citation: Pancreas. 2000 Apr;20(3):217-26
references.pmid: 10766446
references.citation: J Biol Chem. 1996 Aug 23;271(34):20223-6
references.pmid: 8702750
references.citation: Biochim Biophys Acta. 1985 Nov 20;847(2):255-62
references.pmid: 2415168
references.citation: J Biol Chem. 1989 Apr 5;264(10):5412-9
references.pmid: 2784433
references.citation: Mol Biol Cell. 2007 Jul;18(7):2473-80
references.pmid: 17442889
references.citation: Arch Biochem Biophys. 2008 Jul 1;475(1):87-92
references.pmid: 18477466
references.citation: Biochem Biophys Res Commun. 2004 Oct 29;323(4):1157-62
references.pmid: 15451418
references.citation: Trends Cell Biol. 2011 Oct;21(10):615-23
references.pmid: 21820312
references.citation: Am J Physiol Cell Physiol. 2011 Aug;301(2):C507-21
references.pmid: 21525430
references.citation: Am J Physiol. 1982 Apr;242(4):G423-8
references.pmid: 6175231
references.citation: EMBO J. 2001 Jun 1;20(11):2680-9
references.pmid: 11387203
references.citation: Front Endocrinol (Lausanne). 2013 Dec 04;4:187
references.pmid: 24363652
references.citation: Cell Mol Life Sci. 2013 Jun;70(12):2099-121
references.pmid: 22986507
references.citation: FEBS Lett. 1984 May 7;170(1):64-8
references.pmid: 6202551
references.citation: Gastroenterology. 2007 Apr;132(4):1527-45
references.pmid: 17408632
references.citation: PLoS One. 2012;7(7):e39815
references.pmid: 22768313
references.citation: Nature. 1998 Sep 24;395(6700):347-53
references.pmid: 9759724
references.citation: Mol Biol Cell. 1996 Dec;7(12):2019-27
references.pmid: 8970162
references.citation: Trends Cell Biol. 2014 Jan;24(1):35-43
references.pmid: 24119662
references.citation: Eur J Cell Biol. 1997 May;73(1):81-92
references.pmid: 9174674
references.citation: Am J Physiol Gastrointest Liver Physiol. 2013 Sep 15;305(6):G439-52
references.pmid: 23868405
references.citation: J Cell Sci. 1999 Jan;112 ( Pt 1):81-96
references.pmid: 9841906
references.citation: Eur J Oral Sci. 2012 Apr;120(2):123-31
references.pmid: 22409218
references.citation: J Clin Invest. 2001 Dec;108(11):1597-611
references.pmid: 11733555
references.citation: Traffic. 2012 Jul;13(7):898-907
references.pmid: 22420621
references.citation: J Biol Chem. 2010 Nov 12;285(46):35558-66
references.pmid: 20829354
references.citation: Am J Physiol Cell Physiol. 2010 May;298(5):C1151-8
references.pmid: 20164376
references.citation: J Cell Sci. 2007 Feb 15;120(Pt 4):617-27
references.pmid: 17264148
references.citation: Gastroenterology. 1996 Dec;111(6):1661-9
references.pmid: 8942747
references.citation: Gastroenterology. 2012 Sep;143(3):832-843.e7
references.pmid: 22710192
references.citation: Crit Rev Oral Biol Med. 1992;3(1-2):83-107
references.pmid: 1730072
references.citation: Yonsei Med J. 2008 Apr 30;49(2):311-21
references.pmid: 18452270
references.citation: Am J Physiol Cell Physiol. 2005 Jul;289(1):C22-32
references.pmid: 15743890
references.citation: Mol Biol Cell. 2011 Jul 1;22(13):2324-36
references.pmid: 21551071
references.citation: J Biol Chem. 1999 Aug 6;274(32):22871-6
references.pmid: 10428873
references.citation: Traffic. 2013 Sep;14(9):949-63
references.pmid: 23678941
references.citation: J Biol Chem. 2007 Mar 30;282(13):9635-9645
references.pmid: 17272274
references.citation: Pflugers Arch. 2004 Aug;448(5):552-5
references.pmid: 15103465
references.citation: Arch Oral Biol. 2001 Oct;46(10):955-62
references.pmid: 11451410
references.citation: J Biol Chem. 1994 Jun 24;269(25):17062-6
references.pmid: 7516331
references.citation: J Biol Chem. 2009 Jul 31;284(31):20840-7
references.pmid: 19487699
references.citation: Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E405-14
references.pmid: 19088252
references.citation: Arch Oral Biol. 2000 May;45(5):369-75
references.pmid: 10739858
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1091-5
references.pmid: 10655489
references.citation: Arch Oral Biol. 2003 Aug;48(8):597-604
references.pmid: 12828989
references.citation: J Biol Chem. 1994 Feb 18;269(7):5328-35
references.pmid: 8106518
references.citation: Nat Rev Mol Cell Biol. 2001 Feb;2(2):98-106
references.pmid: 11252968
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):E3271-80
references.pmid: 23918365
references.citation: Dev Cell. 2004 Sep;7(3):359-71
references.pmid: 15363411