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 (https://doi.org/10.1242/jcs.212498)

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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 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)