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J Cell Sci. 2018 Oct 22;131(20). pii: jcs212498. doi: 10.1242/jcs.212498.

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

Author information

1
Department of Biomedical Science, Centre for Membrane Interactions and Dynamics, University of Sheffield, Firth Court, Sheffield S10 2TN, UK.
2
Faculty of Health and Life Sciences, Coventry University, Science and Health Building, 20 Whitefriars Street, Coventry CV1 2DS, UK.
3
Faculty of Medicine and Health Sciences, University Sains Islam Malaysia, 55700 Kuala Lumpur, Malaysia.
4
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK.
5
Faculty of Science, Mass Spectrometry Centre, University of Sheffield, Brook Hill Road, Sheffield S3 7HF, UK.
6
Department of Biomedical Science, Centre for Membrane Interactions and Dynamics, University of Sheffield, Firth Court, Sheffield S10 2TN, UK a.peden@sheffield.ac.uk.

Abstract

STX19 is an unusual Qa-SNARE as it lacks a C-terminal transmembrane domain. However, it is efficiently targeted to post-Golgi membranes. Here, we 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 colocalises with MICAL-L1 and Rab8 (which has Rab8a and Rab8b forms). 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.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

MICAL-L1; Palmitoylation; Rab8; S-acylation; SNARE; STX19

PMID:
30254024
DOI:
10.1242/jcs.212498
[Indexed for MEDLINE]
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