S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19

Khamal K Ampah, Jennifer Greaves, Amber S M Shun-Shion, Asral W B A Asnawi, Jessica A Lidster, Luke H Chamberlain, Mark O Collins, Andrew A Peden

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Abstract

STX19 is an unusual Qa-SNARE as it lacks a C-terminal transmembrane domain. However, it is efficiently targeted to post-Golgi membranes. We have set out to determine the intracellular localisation of endogenous STX19 and elucidate the mechanism by which it is targeted to membranes. We have found that a pool of STX19 is localised to tubular recycling endosomes where it co-localises with MICAL-L1 and Rab8. Using a combination of genetic, biochemical and cell based approaches we have identified that STX19 is S-acylated at its C-terminus and is a substrate for several Golgi localised S-acyltransferases, suggesting that STX19 is initially S-acylated at the Golgi before trafficking to the plasma membrane and endosomes. Surprisingly, we have found that S-acylation is a key determinant in targeting STX19 to tubular recycling endosomes, suggesting that S-acylation may play a general role in directing proteins to this compartment. In addition, S-acylation also protects STX19 from proteosomal degradation indicating that S-acylation regulates the function of STX19 at multiple levels.

Original languageEnglish
Article number jcs212498
Number of pages48
JournalJournal of Cell Science
Volume131
Issue number20
Early online date25 Sep 2018
DOIs
Publication statusPublished - 22 Oct 2018

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Q-SNARE Proteins
Acylation
Endosomes
Qa-SNARE Proteins
Acyltransferases
Membranes
Molecular Biology
Cell Membrane
Proteins

Bibliographical note

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

Keywords

  • Journal Article

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Ampah, K. K., Greaves, J., Shun-Shion, A. S. M., Asnawi, A. W. B. A., Lidster, J. A., Chamberlain, L. H., ... Peden, A. A. (2018). S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. Journal of Cell Science, 131(20), [ jcs212498]. https://doi.org/10.1242/jcs.212498

S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. / Ampah, Khamal K; Greaves, Jennifer; Shun-Shion, Amber S M; Asnawi, Asral W B A; Lidster, Jessica A; Chamberlain, Luke H; Collins, Mark O; Peden, Andrew A.

In: Journal of Cell Science, Vol. 131, No. 20, jcs212498, 22.10.2018.

Research output: Contribution to journalArticle

Ampah, KK, Greaves, J, Shun-Shion, ASM, Asnawi, AWBA, Lidster, JA, Chamberlain, LH, Collins, MO & Peden, AA 2018, 'S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19' Journal of Cell Science, vol. 131, no. 20, jcs212498. https://doi.org/10.1242/jcs.212498
Ampah KK, Greaves J, Shun-Shion ASM, Asnawi AWBA, Lidster JA, Chamberlain LH et al. S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. Journal of Cell Science. 2018 Oct 22;131(20). jcs212498. https://doi.org/10.1242/jcs.212498
Ampah, Khamal K ; Greaves, Jennifer ; Shun-Shion, Amber S M ; Asnawi, Asral W B A ; Lidster, Jessica A ; Chamberlain, Luke H ; Collins, Mark O ; Peden, Andrew A. / S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. In: Journal of Cell Science. 2018 ; Vol. 131, No. 20.
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