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PMID: 9693380 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cysteine string protein functions directly in regulated exocytosis.

Molecular biology of the cell ·Vol. 9 ·No. 8 ·1998-08-00 ·Pages 2259-67

Chamberlain LH, Burgoyne RD

Abstract

Cysteine string protein (Csp) is essential for neurotransmitter release in Drosophila. It has been suggested that Csp functions by regulating the activity of presynaptic Ca2+ channels, thus controlling exocytosis. We have examined the effect of overexpressing Csp1 in PC12 cells, a neuroendocrine cell line. PC12 cell clones overexpressing Csp1 did not show any changes in morphology, granule number or distribution, or in the levels of other key exocytotic proteins. This overexpression did not affect intracellular Ca2+ signals after depolarization, suggesting that Csp1 has no gross effect on Ca2+ channel activity in PC12 cells. In contrast, we show that Csp1 overexpression enhances the extent of exocytosis from permeabilized cells in response to Ca2+ or GTPgammaS in the absence of Ca2+. Because secretion from permeabilized cells is not influenced by Ca2+ channel activity, this represents the first demonstration that Csp has a direct role in regulated exocytosis.

MeSH Terms
Animals Calcium/metabolism Cell Fractionation Cell Membrane/metabolism,ultrastructure Clone Cells Dopamine/metabolism Exocytosis HSP40 Heat-Shock Proteins Homeostasis Kinetics Membrane Proteins Nerve Tissue Proteins/biosynthesis,metabolism PC12 Cells Rats Recombinant Proteins/biosynthesis,metabolism Signal Transduction Transfection
Chemicals
HSP40 Heat-Shock Proteins Membrane Proteins Nerve Tissue Proteins Recombinant Proteins cysteine string protein Calcium Dopamine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chamberlain L H
The Physiological Laboratory, Liverpool University, Liverpool L69 3BX, United Kingdom.
Burgoyne R D
References (36)
36 references, click to expand
  1. The molecular chaperone function of the secretory vesicle cysteine string proteins.
    J Biol Chem. 1997 Dec 12;272(50):31420-6 PMID: 9395474
  2. Redistribution of synaptic vesicles and their proteins in temperature-sensitive shibire(ts1) mutant Drosophila.
    Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5739-43 PMID: 7777578
  3. Escherichia coli dnaJ deletion mutation results in loss of stability of a positive regulator, CRP.
    J Biol Chem. 1992 Jul 5;267(19):13180-4 PMID: 1618821
  4. SNAP-25 is present in a SNARE complex in adrenal chromaffin cells.
    FEBS Lett. 1994 Sep 5;351(2):207-10 PMID: 8082766
  5. Classic clues to NSF function.
    Nature. 1996 Aug 22;382(6593):680 PMID: 8751437
  6. Association of Drosophila cysteine string proteins with membranes.
    FEBS Lett. 1996 Feb 19;380(3):251-6 PMID: 8601435
  7. Presynaptic dysfunction in Drosophila csp mutants.
    Neuron. 1994 Oct;13(4):899-907 PMID: 7946336
  8. Widespread expression of human cysteine string proteins.
    FEBS Lett. 1996 Aug 12;391(3):269-72 PMID: 8764987
  9. The nucleotide and deduced amino acid sequence of a rat cysteine string protein.
    Brain Res Mol Brain Res. 1995 Jan;28(1):12-8 PMID: 7535880
  10. Evidence that cysteine string proteins regulate an early step in the Ca2+-dependent secretion of neurotransmitter at Drosophila neuromuscular junctions.
    J Neurosci. 1997 Oct 1;17(19):7203-9 PMID: 9295366
  11. Nerve growth factor modulates the drug sensitivity of neurotransmitter release from PC-12 cells.
    Proc Natl Acad Sci U S A. 1986 Apr;83(7):2243-7 PMID: 2421290
  12. MgATP-independent and MgATP-dependent exocytosis. Evidence that MgATP primes adrenal chromaffin cells to undergo exocytosis.
    J Biol Chem. 1989 Apr 5;264(10):5412-9 PMID: 2784433
  13. A Drosophila NSF mutant.
    Nature. 1995 Jul 6;376(6535):25 PMID: 7596428
  14. Molecular analysis of the para locus, a sodium channel gene in Drosophila.
    Cell. 1989 Sep 22;58(6):1143-54 PMID: 2550145
  15. Cysteine string proteins: a potential link between synaptic vesicles and presynaptic Ca2+ channels.
    Science. 1994 Feb 18;263(5149):981-2 PMID: 7906056
  16. The synaptic vesicle cycle: a cascade of protein-protein interactions.
    Nature. 1995 Jun 22;375(6533):645-53 PMID: 7791897
  17. The cysteine string secretory vesicle protein activates Hsc70 ATPase.
    J Biol Chem. 1996 Oct 18;271(42):25989-93 PMID: 8824236
  18. Sec18p (NSF)-driven release of Sec17p (alpha-SNAP) can precede docking and fusion of yeast vacuoles.
    Cell. 1996 Apr 5;85(1):83-94 PMID: 8620540
  19. A cysteine-string protein is expressed in retina and brain of Drosophila.
    J Neurogenet. 1990 Nov;7(1):15-29 PMID: 2129171
  20. Distinct effects of alpha-SNAP, 14-3-3 proteins, and calmodulin on priming and triggering of regulated exocytosis.
    J Cell Biol. 1995 Sep;130(5):1063-70 PMID: 7657692
  21. Evoked transmitter release at neuromuscular junctions in wild type and cysteine string protein null mutant larvae of Drosophila.
    Neurosci Lett. 1997 Jun 13;228(3):167-70 PMID: 9218634
  22. Cysteine string proteins associated with secretory granules of the rat neurohypophysis.
    J Neurosci. 1997 Apr 15;17(8):2722-7 PMID: 9092593
  23. Resolution of regulated secretion into sequential MgATP-dependent and calcium-dependent stages mediated by distinct cytosolic proteins.
    J Cell Biol. 1992 Oct;119(1):139-51 PMID: 1527165
  24. Paralysis and early death in cysteine string protein mutants of Drosophila.
    Science. 1994 Feb 18;263(5149):977-80 PMID: 8310297
  25. Neurophysiological defects in temperature-sensitive paralytic mutants of Drosophila melanogaster.
    Proc Natl Acad Sci U S A. 1976 Sep;73(9):3253-7 PMID: 184469
  26. Suppression cloning of the cDNA for a candidate subunit of a presynaptic calcium channel.
    Neuron. 1992 Sep;9(3):527-37 PMID: 1326297
  27. Effects of calcium channel antagonists on calcium entry and glutamate release from cultured rat cerebellar granule cells.
    J Neurochem. 1995 Dec;65(6):2517-24 PMID: 7595546
  28. Is NSF a fusion protein?
    Trends Cell Biol. 1995 Sep;5(9):335-9 PMID: 14732068
  29. Activation of the ATPase activity of heat-shock proteins Hsc70/Hsp70 by cysteine-string protein.
    Biochem J. 1997 Mar 15;322 ( Pt 3):853-8 PMID: 9148760
  30. Cysteine string protein is required for calcium secretion coupling of evoked neurotransmission in drosophila but not for vesicle recycling.
    J Neurosci. 1998 Feb 1;18(3):956-64 PMID: 9437017
  31. Cysteine string protein, a DnaJ family member, is present on diverse secretory vesicles.
    Neuropharmacology. 1995 Nov;34(11):1361-9 PMID: 8606785
  32. Modification of annexin II expression in PC12 cell lines does not affect Ca(2+)-dependent exocytosis.
    Mol Biol Cell. 1997 Mar;8(3):431-42 PMID: 9188096
  33. Neuronal differentiation of Ca2+ channel by nerve growth factor.
    Brain Res. 1985 Aug 26;341(2):381-4 PMID: 2412637
  34. Extensive lipidation of a Torpedo cysteine string protein.
    J Biol Chem. 1994 Jul 29;269(30):19197-9 PMID: 8034679
  35. Cysteine string proteins are associated with chromaffin granules.
    J Biol Chem. 1996 Aug 9;271(32):19514-7 PMID: 8702643
  36. Identification of a novel cysteine string protein variant and expression of cysteine string proteins in non-neuronal cells.
    J Biol Chem. 1996 Mar 29;271(13):7320-3 PMID: 8631751
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
Published
1998-08-00
Pages
2259-67
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25479
Subset
IM
Grants
Wellcome Trust · United Kingdom
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