Impaired Recycling of Synaptic Vesicles After Acute Perturbation of the Presynaptic Actin Cytoskeleton

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2002 Oct 17

PMID 12381791

Citations 94

Authors

Oleg Shupliakov

Ona Bloom

Jenny S Gustafsson

Ole Kjaerulff

Peter Low

Nikolay Tomilin

Vincent A Pieribone

Paul Greengard

Lennart Brodin

Affiliations

Soon will be listed here.

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.

Citing Articles

Condensates of synaptic vesicles and synapsin are molecular beacons for actin sequestering and polymerization.

Akshita C, Christian H, Aleksandr K, Jakob R, Linda K, Luka G bioRxiv. 2024; .

PMID: 39071264 PMC: 11275919. DOI: 10.1101/2024.07.19.604346.

Rho GTPase signaling and mDia facilitate endocytosis via presynaptic actin.

Oevel K, Hohensee S, Kumar A, Rosas-Brugada I, Bartolini F, Soykan T Elife. 2024; 12.

PMID: 38502163 PMC: 10950329. DOI: 10.7554/eLife.92755.

Membrane transformations of fusion and budding.

Wu L, Chan C Nat Commun. 2024; 15(1):21.

PMID: 38167896 PMC: 10761761. DOI: 10.1038/s41467-023-44539-7.

Dipping contacts - a novel type of contact site at the interface between membraneless organelles and membranes.

Hoffmann C, Milovanovic D J Cell Sci. 2023; 136(24).

PMID: 38149872 PMC: 10785658. DOI: 10.1242/jcs.261413.

Presynapses contain distinct actin nanostructures.

Bingham D, Jakobs C, Wernert F, Boroni-Rueda F, Jullien N, Schentarra E J Cell Biol. 2023; 222(10).

PMID: 37578754 PMC: 10424573. DOI: 10.1083/jcb.202208110.

References

Cremona O, Di Paolo G, Wenk M, Luthi A, Kim W, Takei K . Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell. 1999; 99(2):179-88. DOI: 10.1016/s0092-8674(00)81649-9. View

Job C, Lagnado L . Calcium and protein kinase C regulate the actin cytoskeleton in the synaptic terminal of retinal bipolar cells. J Cell Biol. 1998; 143(6):1661-72. PMC: 2132988. DOI: 10.1083/jcb.143.6.1661. View

Roos J, Kelly R . The endocytic machinery in nerve terminals surrounds sites of exocytosis. Curr Biol. 1999; 9(23):1411-4. DOI: 10.1016/s0960-9822(00)80087-1. View

Ringstad N, Gad H, Low P, Di Paolo G, Brodin L, Shupliakov O . Endophilin/SH3p4 is required for the transition from early to late stages in clathrin-mediated synaptic vesicle endocytosis. Neuron. 2000; 24(1):143-54. DOI: 10.1016/s0896-6273(00)80828-4. View

Rozelle A, Machesky L, Yamamoto M, Driessens M, Insall R, Roth M . Phosphatidylinositol 4,5-bisphosphate induces actin-based movement of raft-enriched vesicles through WASP-Arp2/3. Curr Biol. 2000; 10(6):311-20. DOI: 10.1016/s0960-9822(00)00384-5. View

Brodin L, Low P, Shupliakov O . Sequential steps in clathrin-mediated synaptic vesicle endocytosis. Curr Opin Neurobiol. 2000; 10(3):312-20. DOI: 10.1016/s0959-4388(00)00097-0. View

Doussau F, Augustine G . The actin cytoskeleton and neurotransmitter release: an overview. Biochimie. 2000; 82(4):353-63. DOI: 10.1016/s0300-9084(00)00217-0. View

Dunaevsky A, Connor E . F-actin is concentrated in nonrelease domains at frog neuromuscular junctions. J Neurosci. 2000; 20(16):6007-12. PMC: 6772601. View

Qualmann B, Kessels M, Kelly R . Molecular links between endocytosis and the actin cytoskeleton. J Cell Biol. 2000; 150(5):F111-6. PMC: 2175242. DOI: 10.1083/jcb.150.5.f111. View

10.

Gad H, Ringstad N, Low P, Kjaerulff O, Gustafsson J, Wenk M . Fission and uncoating of synaptic clathrin-coated vesicles are perturbed by disruption of interactions with the SH3 domain of endophilin. Neuron. 2000; 27(2):301-12. DOI: 10.1016/s0896-6273(00)00038-6. View

11.

Taunton J . Actin filament nucleation by endosomes, lysosomes and secretory vesicles. Curr Opin Cell Biol. 2001; 13(1):85-91. DOI: 10.1016/s0955-0674(00)00178-2. View

12.

Fujimoto L, Roth R, Heuser J, Schmid S . Actin assembly plays a variable, but not obligatory role in receptor-mediated endocytosis in mammalian cells. Traffic. 2001; 1(2):161-71. DOI: 10.1034/j.1600-0854.2000.010208.x. View

13.

Slepnev V, De Camilli P . Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nat Rev Neurosci. 2001; 1(3):161-72. DOI: 10.1038/35044540. View

14.

Jarousse N, Kelly R . Endocytotic mechanisms in synapses. Curr Opin Cell Biol. 2001; 13(4):461-9. DOI: 10.1016/s0955-0674(00)00237-4. View

15.

Jeng R, Welch M . Cytoskeleton: actin and endocytosis--no longer the weakest link. Curr Biol. 2001; 11(17):R691-4. DOI: 10.1016/s0960-9822(01)00410-9. View

16.

Wenk M, Pellegrini L, Klenchin V, Di Paolo G, Chang S, Daniell L . PIP kinase Igamma is the major PI(4,5)P(2) synthesizing enzyme at the synapse. Neuron. 2001; 32(1):79-88. DOI: 10.1016/s0896-6273(01)00456-1. View

17.

Lee E, De Camilli P . Dynamin at actin tails. Proc Natl Acad Sci U S A. 2002; 99(1):161-6. PMC: 117532. DOI: 10.1073/pnas.012607799. View

18.

Orth J, Krueger E, Cao H, McNiven M . The large GTPase dynamin regulates actin comet formation and movement in living cells. Proc Natl Acad Sci U S A. 2002; 99(1):167-72. PMC: 117533. DOI: 10.1073/pnas.012607899. View

19.

Higgs H, Pollard T . Regulation of actin filament network formation through ARP2/3 complex: activation by a diverse array of proteins. Annu Rev Biochem. 2001; 70:649-76. DOI: 10.1146/annurev.biochem.70.1.649. View

20.

Guichet A, Wucherpfennig T, Dudu V, Etter S, Hellwig A, Gonzalez-Gaitan M . Essential role of endophilin A in synaptic vesicle budding at the Drosophila neuromuscular junction. EMBO J. 2002; 21(7):1661-72. PMC: 125961. DOI: 10.1093/emboj/21.7.1661. View