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Published on: December 6, 2019
A novel syntaxin 6-interacting protein, SHIP164, regulates syntaxin 6-dependent sorting from early endosomes
Grant P Otto1, Minoo Razi, Jöelle Morvan
1Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London, UK.
Researchers identified SHIP164, a protein involved in regulating membrane fusion. SHIP164 interacts with the Syntaxin 6 Habc domain and influences endosomal trafficking, impacting receptor transport.
Area of Science:
- Cell Biology
- Molecular Biology
- Membrane Trafficking
Background:
- Membrane fusion relies on SNARE proteins and their alpha-helical SNARE motifs forming SNARE complexes.
- Habc domains of SNAREs interact with other proteins, suggesting a regulatory role in membrane fusion.
Purpose of the Study:
- To identify proteins interacting with the Habc domain of Syntaxin 6.
- To characterize the function of a newly identified protein, SHIP164, in cellular trafficking.
Main Methods:
- Screening for proteins interacting with Syntaxin 6 Habc domain.
- Co-immunoprecipitation and complex analysis to identify interacting partners.
- Depletion and overexpression studies to assess protein function.
- Analysis of endosomal morphology and receptor transport.
Main Results:
- A novel 164-kDa protein, SHIP164, was identified and found to be part of a ~700 kDa complex.
- SHIP164 interacts with the Golgi-associated retrograde protein (GARP) tethering complex.
- SHIP164 localization is dependent on GARP subunits and Syntaxin 6 levels.
- SHIP164 overexpression with Syntaxin 6 causes endosomal tubulation and disrupts cation-independent mannose-6-phosphate receptor (CI-MPR) and transferrin receptor transport.
Conclusions:
- SHIP164 is a novel protein functioning in the early/recycling endosomal system.
- SHIP164 plays a regulatory role in membrane trafficking pathways.
- SHIP164's function is linked to the GARP tethering complex and Syntaxin 6.
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