Home LiteratureArticle Details
PMID: 9618556 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Modulation of an early step in the secretory machinery in hippocampal nerve terminals.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 12 ·1998-06-09 ·Pages 7163-8

Trudeau LE, Fang Y, Haydon PG

Abstract

In hippocampal neurons, neurotransmitter release can be regulated by protein kinase A (PKA) through a direct action on the secretory machinery. To identify the site of PKA modulation, we have taken advantage of the ability of the neurotoxin Botulinum A to cleave the synaptic protein SNAP-25. Cleavage of this protein decreases the Ca2+ responsiveness of the secretory machinery by partially uncoupling Ca2+-sensing from fusion per se. This is expressed as a shift toward higher Ca2+ levels of the Ca2+ to neurotransmitter release relationship and as a perturbation of synaptic delay under conditions where secretion induced by the Ca2+-independent secretagogue ruthenium red is unimpaired. We find that SNAP-25 cleavage also perturbs PKA-dependent modulation of secretion; facilitation of ruthenium red-evoked neurotransmitter release by the adenylyl cyclase activator forskolin is blocked completely after Botulinum toxin A action. Together with our observation that forskolin modifies the Ca2+ to neurotransmitter release relationship, our results suggest that SNAP-25 acts as a functional linker between Ca2+ detection and fusion and that PKA modulates an early step in the secretory machinery related to calcium sensing to facilitate synaptic transmission.

MeSH Terms
Animals Botulinum Toxins, Type A/toxicity Calcium/physiology Cyclic AMP-Dependent Protein Kinases/physiology Electrophysiology Hippocampus/cytology,physiology Membrane Proteins Nerve Tissue Proteins/physiology Neuromuscular Agents/toxicity Rats Synapses/physiology Synaptic Transmission/drug effects,physiology Synaptosomal-Associated Protein 25
Chemicals
Membrane Proteins Nerve Tissue Proteins Neuromuscular Agents Snap25 protein, rat Synaptosomal-Associated Protein 25 Cyclic AMP-Dependent Protein Kinases Botulinum Toxins, Type A Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Trudeau L E
Laboratory of Cellular Signaling, Department of Zoology and Genetics, Iowa State University, Ames, IA 50011, USA. Trudeal@ere.umontreal.ca
Fang Y
Haydon P G
References (28)
28 references, click to expand
  1. Co-operative action a calcium ions in transmitter release at the neuromuscular junction.
    J Physiol. 1967 Nov;193(2):419-32 PMID: 6065887
  2. Muscarinic stimulation of synaptic activity by protein kinase C is inhibited by adenosine in cultured hippocampal neurons.
    Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12224-9 PMID: 9342390
  3. Divalent cations differentially support transmitter release at the squid giant synapse.
    J Physiol. 1984 Jan;346:257-71 PMID: 6142104
  4. Transmission at voltage-clamped giant synapse of the squid: evidence for cooperativity of presynaptic calcium action.
    Proc Natl Acad Sci U S A. 1985 Jan;82(2):622-5 PMID: 2982166
  5. Decline in calcium cooperativity as the basis of facilitation at the squid giant synapse.
    J Neurosci. 1986 Mar;6(3):782-9 PMID: 2870141
  6. Differential effects of various secretagogues on quantal transmitter release from mouse motor nerve terminals treated with botulinum A and tetanus toxin.
    Naunyn Schmiedebergs Arch Pharmacol. 1987 Jan;335(1):1-7 PMID: 2883583
  7. A study of synchronization of quantal transmitter release from mammalian motor endings by the use of botulinal toxins type A and D.
    J Physiol. 1989 Apr;411:195-205 PMID: 2575665
  8. Altered synaptic plasticity in Drosophila memory mutants with a defective cyclic AMP cascade.
    Science. 1991 Jan 11;251(4990):198-201 PMID: 1670967
  9. Ca(2+)-independent and Ca(2+)-dependent stimulation of quantal neurosecretion in avian ciliary ganglion neurons.
    J Neurophysiol. 1992 Oct;68(4):1229-34 PMID: 1432080
  10. A synaptic model of memory: long-term potentiation in the hippocampus.
    Nature. 1993 Jan 7;361(6407):31-9 PMID: 8421494
  11. Increased transmitter release at excitatory synapses produced by direct activation of adenylate cyclase in rat hippocampal slices.
    J Neurosci. 1994 Jan;14(1):310-7 PMID: 7506766
  12. Synaptic augmentation by 5-HT at rested Aplysia sensorimotor synapses: independence of action potential prolongation.
    Neuron. 1994 Jul;13(1):159-66 PMID: 7913820
  13. Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP.
    Science. 1994 Sep 23;265(5180):1878-82 PMID: 7916482
  14. Clostridial neurotoxins as tools to investigate the molecular events of neurotransmitter release.
    Semin Cell Biol. 1994 Aug;5(4):221-9 PMID: 7994006
  15. Presynaptic enhancement of inhibitory synaptic transmission by protein kinases A and C in the rat hippocampus in vitro.
    J Neurosci. 1995 Feb;15(2):1249-60 PMID: 7869096
  16. Phosphorylation of rabphilin-3A by Ca2+/calmodulin- and cAMP-dependent protein kinases in vitro.
    J Neurosci. 1995 Mar;15(3 Pt 2):2385-95 PMID: 7891174
  17. Contrasting properties of two forms of long-term potentiation in the hippocampus.
    Nature. 1995 Sep 14;377(6545):115-8 PMID: 7675078
  18. Molecular aspects of tetanus and botulinum neurotoxin poisoning.
    Prog Neurobiol. 1995 May;46(1):83-96 PMID: 7568911
  19. Calcium-independent activation of the secretory apparatus by ruthenium red in hippocampal neurons: a new tool to assess modulation of presynaptic function.
    J Neurosci. 1996 Jan;16(1):46-54 PMID: 8613808
  20. Long-term potentiation and learning.
    Annu Rev Psychol. 1996;47:173-203 PMID: 8624136
  21. Definition of the readily releasable pool of vesicles at hippocampal synapses.
    Neuron. 1996 Jun;16(6):1197-207 PMID: 8663996
  22. Phosphorylation of 25-kDa synaptosome-associated protein. Possible involvement in protein kinase C-mediated regulation of neurotransmitter release.
    J Biol Chem. 1996 Jun 14;271(24):14548-53 PMID: 8662851
  23. Phosphorylation of synaptic vesicle proteins: modulation of the alpha SNAP interaction with the core complex.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11945-9 PMID: 8876242
  24. Direct modulation of the secretory machinery underlies PKA-dependent synaptic facilitation in hippocampal neurons.
    Neuron. 1996 Oct;17(4):789-97 PMID: 8893035
  25. Rab3A is essential for mossy fibre long-term potentiation in the hippocampus.
    Nature. 1997 Aug 7;388(6642):590-3 PMID: 9252190
  26. Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion.
    Nature. 1997 Aug 7;388(6642):593-8 PMID: 9252191
  27. Ca2+ or Sr2+ partially rescues synaptic transmission in hippocampal cultures treated with botulinum toxin A and C, but not tetanus toxin.
    J Neurosci. 1997 Oct 1;17(19):7190-202 PMID: 9295365
  28. Role of presynaptic calcium ions and channels in synaptic facilitation and depression at the squid giant synapse.
    J Physiol. 1982 Feb;323:173-93 PMID: 6284915
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.12.7163
Email
trudeal@ere.umontreal.ca
Published
1998-06-09
Pages
7163-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22774
Subset
IM
Grants
NINDS NIH HHS · NS24233 · United States
NINDS NIH HHS · NS26650 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.12.7163 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2