Intra-membrane Signaling Between the Voltage-gated Ca2+-channel and Cysteine Residues of Syntaxin 1A Coordinates Synchronous Release

Overview

Journal Sci Rep

Specialty Science

Date 2013 Apr 10

PMID 23567899

Citations 11

Authors

Niv Bachnoff

Moshe Cohen-Kutner

Michael Trus

Daphne Atlas

Affiliations

Soon will be listed here.

Abstract

The interaction of syntaxin 1A (Sx1A) with voltage-gated calcium channels (VGCC) is required for depolarization-evoked release. However, it is unclear how the signal is transferred from the channel to the exocytotic machinery and whether assembly of Sx1A and the calcium channel is conformationally linked to triggering synchronous release. Here we demonstrate that depolarization-evoked catecholamine release was decreased in chromaffin cells infected with semliki forest viral vectors encoding Sx1A mutants, Sx1A(C271V), or Sx1A(C272V), or by direct oxidation of these Sx1A transmembrane (TM) cysteine residues. Mutating or oxidizing these highly conserved Sx1A Cys271 and Cys272 equally disrupted the Sx1A interaction with the channel. The results highlight the functional link between the VGCC and the exocytotic machinery, and attribute the redox sensitivity of the release process to the Sx1A TM C271 and C272. This unique intra-membrane signal-transduction pathway enables fast signaling, and triggers synchronous release by conformational-coupling of the channel with Sx1A.

Citing Articles

Non-ionotropic voltage-gated calcium channel signaling.

Trus M, Atlas D Channels (Austin). 2024; 18(1):2341077.

PMID: 38601983 PMC: 11017947. DOI: 10.1080/19336950.2024.2341077.

The bs5 allele of the susceptibility gene Bs5 of pepper (Capsicum annuum L.) encoding a natural deletion variant of a CYSTM protein conditions resistance to bacterial spot disease caused by Xanthomonas species.

Szabo Z, Balogh M, Domonkos A, Csanyi M, Kalo P, Kiss G Theor Appl Genet. 2023; 136(3):64.

PMID: 36943531 PMC: 10030403. DOI: 10.1007/s00122-023-04340-y.

Presynaptic Acetylcholine Receptors Modulate the Time Course of Action Potential-Evoked Acetylcholine Quanta Secretion at Neuromuscular Junctions.

Bukharaeva E, Skorinkin A, Samigullin D, Petrov A Biomedicines. 2022; 10(8).

PMID: 35892671 PMC: 9332499. DOI: 10.3390/biomedicines10081771.

Syntaxin-1A modulates vesicle fusion in mammalian neurons via juxtamembrane domain dependent palmitoylation of its transmembrane domain.

Vardar G, Salazar-Lazaro A, Zobel S, Trimbuch T, Rosenmund C Elife. 2022; 11.

PMID: 35638903 PMC: 9183232. DOI: 10.7554/eLife.78182.

Reexamination of N-terminal domains of syntaxin-1 in vesicle fusion from central murine synapses.

Vardar G, Salazar-Lazaro A, Brockmann M, Weber-Boyvat M, Zobel S, Kumbol V Elife. 2021; 10.

PMID: 34427183 PMC: 8416022. DOI: 10.7554/eLife.69498.

References

von Heijne G . Membrane proteins up for grabs. Nat Biotechnol. 2007; 25(6):646-7. DOI: 10.1038/nbt0607-646. View

RETTIG J, Sheng Z, Kim D, Hodson C, Snutch T, Catterall W . Isoform-specific interaction of the alpha1A subunits of brain Ca2+ channels with the presynaptic proteins syntaxin and SNAP-25. Proc Natl Acad Sci U S A. 1996; 93(14):7363-8. PMC: 38990. DOI: 10.1073/pnas.93.14.7363. View

Offen D, Gilgun-Sherki Y, Barhum Y, Benhar M, Grinberg L, Reich R . A low molecular weight copper chelator crosses the blood-brain barrier and attenuates experimental autoimmune encephalomyelitis. J Neurochem. 2004; 89(5):1241-51. DOI: 10.1111/j.1471-4159.2004.02428.x. View

Wightman R, Jankowski J, Kennedy R, Kawagoe K, Schroeder T, Leszczyszyn D . Temporally resolved catecholamine spikes correspond to single vesicle release from individual chromaffin cells. Proc Natl Acad Sci U S A. 1991; 88(23):10754-8. PMC: 53009. DOI: 10.1073/pnas.88.23.10754. View

Arkin I, Adams P, Brunger A, Aimoto S, Engelman D, Smith S . Structure of the transmembrane cysteine residues in phospholamban. J Membr Biol. 1997; 155(3):199-206. DOI: 10.1007/s002329900172. View

Cohen R, Marom M, Atlas D . Depolarization-evoked secretion requires two vicinal transmembrane cysteines of syntaxin 1A. PLoS One. 2007; 2(12):e1273. PMC: 2094736. DOI: 10.1371/journal.pone.0001273. View

Hagalili Y, Bachnoff N, Atlas D . The voltage-gated Ca(2+) channel is the Ca(2+) sensor protein of secretion. Biochemistry. 2008; 47(52):13822-30. DOI: 10.1021/bi801619f. View

Bachnoff N, Trus M, Atlas D . Alleviation of oxidative stress by potent and selective thioredoxin-mimetic peptides. Free Radic Biol Med. 2011; 50(10):1355-67. DOI: 10.1016/j.freeradbiomed.2011.02.026. View

Barg S, Knowles M, Chen X, Midorikawa M, Almers W . Syntaxin clusters assemble reversibly at sites of secretory granules in live cells. Proc Natl Acad Sci U S A. 2010; 107(48):20804-9. PMC: 2996446. DOI: 10.1073/pnas.1014823107. View

10.

Cohen R, Atlas D . R-type voltage-gated Ca(2+) channel interacts with synaptic proteins and recruits synaptotagmin to the plasma membrane of Xenopus oocytes. Neuroscience. 2004; 128(4):831-41. DOI: 10.1016/j.neuroscience.2004.07.027. View

11.

PRIOR I, Clague M . Detection of thiol modification following generation of reactive nitrogen species: analysis of synaptic vesicle proteins. Biochim Biophys Acta. 2000; 1475(3):281-6. DOI: 10.1016/s0304-4165(00)00078-7. View

12.

Bezprozvanny I, Zhong P, Scheller R, Tsien R . Molecular determinants of the functional interaction between syntaxin and N-type Ca2+ channel gating. Proc Natl Acad Sci U S A. 2000; 97(25):13943-8. PMC: 17680. DOI: 10.1073/pnas.220389697. View

13.

Atlas D . The voltage-gated calcium channel functions as the molecular switch of synaptic transmission. Annu Rev Biochem. 2013; 82:607-35. DOI: 10.1146/annurev-biochem-080411-121438. View

14.

Breckenridge L, Almers W . Currents through the fusion pore that forms during exocytosis of a secretory vesicle. Nature. 1987; 328(6133):814-7. DOI: 10.1038/328814a0. View

15.

Arkin I, Russ W, Lebendiker M, Schuldiner S . Determining the secondary structure and orientation of EmrE, a multi-drug transporter, indicates a transmembrane four-helix bundle. Biochemistry. 1996; 35(22):7233-8. DOI: 10.1021/bi960094i. View

16.

Venancio T, Aravind L . CYSTM, a novel cysteine-rich transmembrane module with a role in stress tolerance across eukaryotes. Bioinformatics. 2009; 26(2):149-52. PMC: 2804304. DOI: 10.1093/bioinformatics/btp647. View

17.

Atlas D, Wiser O, Trus M . The voltage-gated Ca2+ channel is the Ca2+ sensor of fast neurotransmitter release. Cell Mol Neurobiol. 2002; 21(6):717-31. PMC: 11533850. DOI: 10.1023/a:1015104105262. View

18.

Tobi D, Wiser O, Trus M, Atlas D . N-type voltage-sensitive calcium channel interacts with syntaxin, synaptotagmin and SNAP-25 in a multiprotein complex. Recept Channels. 1999; 6(2):89-98. View

19.

SNYDER R, Mirabelli C, Crooke S . The cellular pharmacology of auranofin. Semin Arthritis Rheum. 1987; 17(1):71-80. DOI: 10.1016/0049-0172(87)90017-5. View

20.

Yamakuchi M, Ferlito M, Morrell C, Matsushita K, Fletcher C, Cao W . Exocytosis of endothelial cells is regulated by N-ethylmaleimide-sensitive factor. Methods Mol Biol. 2008; 440:203-15. PMC: 2846407. DOI: 10.1007/978-1-59745-178-9_15. View