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PMID: 12381791 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Impaired recycling of synaptic vesicles after acute perturbation of the presynaptic actin cytoskeleton.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 22 ·2002-10-29 ·Pages 14476-81

Shupliakov O, Bloom O, Gustafsson JS, Kjaerulff O, Low P, Tomilin N, Pieribone VA, Greengard P, Brodin L

Abstract

Actin is an abundant component of nerve terminals that has been implicated at multiple steps of the synaptic vesicle cycle, including reversible anchoring, exocytosis, and recycling of synaptic vesicles. In the present study we used the lamprey reticulospinal synapse to examine the role of actin at the site of synaptic vesicle recycling, the endocytic zone. Compounds interfering with actin function, including phalloidin, the catalytic subunit of Clostridium botulinum C2 toxin, and N-ethylmaleimide-treated myosin S1 fragments were microinjected into the axon. In unstimulated, phalloidin-injected axons actin filaments formed a thin cytomatrix adjacent to the plasma membrane around the synaptic vesicle cluster. The filaments proliferated after stimulation and extended toward the vesicle cluster. Synaptic vesicles were tethered along the filaments. Injection of N-ethylmaleimide-treated myosin S1 fragments caused accumulation of aggregates of synaptic vesicles between the endocytic zone and the vesicle cluster, suggesting that vesicle transport was inhibited. Phalloidin, as well as C2 toxin, also caused changes in the structure of clathrin-coated pits in stimulated synapses. Our data provide evidence for a critical role of actin in recycling of synaptic vesicles, which seems to involve functions both in endocytosis and in the transport of recycled vesicles to the synaptic vesicle cluster.

MeSH Terms
Actin Cytoskeleton/metabolism Actins/metabolism Animals Botulinum Toxins/pharmacology Cytoskeleton/metabolism Endocytosis/drug effects Lampreys Myosin Subfragments/pharmacology Presynaptic Terminals/drug effects,metabolism Synaptic Vesicles/drug effects
Chemicals
Actins Myosin Subfragments Botulinum Toxins botulinum toxin type C
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Shupliakov Oleg
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
Bloom Ona
Gustafsson Jenny S
Kjaerulff Ole
Low Peter
Tomilin Nikolay
Pieribone Vincent A
Greengard Paul
Brodin Lennart
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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.212381799
Published
2002-10-29
Epub
2002-00-15
Pages
14476-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC137908
Subset
IM
Grants
NIGMS NIH HHS · GM 07982 · United States
NINDS NIH HHS · R01 NS037823 · United States
NIMH NIH HHS · MH 39327 · United States
NIMH NIH HHS · R37 MH039327 · United States
NIMH NIH HHS · R01 MH039327 · United States
NIGMS NIH HHS · T32 GM007982 · United States
External Links
PubMed source DOI: 10.1073/pnas.212381799 PMC Full Text View journal details
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