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

Ampah, Khamal K. and Greaves, Jennifer and Shun-Shion, Amber S. M. and Asnawi, Asral W. B. A. and Lidster, Jessica A. and Chamberlain, Luke H. and Collins, Mark O. and Peden, Andrew A. (2018) S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. Journal of Cell Science. ISSN 0021-9533

[thumbnail of Ampah-etal-JCS2018-S-acylation-regulates-the-trafficking-and-stability-of-the-unconventional]
Preview
 Text (Ampah-etal-JCS2018-S-acylation-regulates-the-trafficking-and-stability-of-the-unconventional)
Ampah_etal_JCS2018_S_acylation_regulates_the_trafficking_and_stability_of_the_unconventional.pdf
Accepted Author Manuscript
License: Creative Commons Attribution 4.0 logo
Download (20MB)| Preview

    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 the 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.

    ORCID iDs

    Ampah, Khamal K., Greaves, Jennifer ORCID logoORCID: https://orcid.org/0000-0001-8445-789X, Shun-Shion, Amber S. M., Asnawi, Asral W. B. A., Lidster, Jessica A., Chamberlain, Luke H. ORCID logoORCID: https://orcid.org/0000-0002-8701-4995, Collins, Mark O. and Peden, Andrew A.;
    CORE (COnnecting REpositories)