Fam20C regulates protein secretion by Cab45 phosphorylation
Tobias Karl-Heinz Hecht1,2, Birgit Blank1,2, Martin Steger2
1Department of Cell Biology, Yale University School of Medicine, New Haven, CT.
The Journal of Cell Biology
|May 19, 2020
Summary
The Golgi-specific protein kinase Fam20C phosphorylates Cab45, a protein involved in sorting and secretion. This phosphorylation promotes the export of Cab45 client proteins from the trans-Golgi network (TGN).
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Trafficking
Background:
- The trans-Golgi network (TGN) is crucial for protein sorting and secretion.
- Soluble protein sorting at the TGN involves oligosaccharide signals or calcium-mediated processes utilizing the cargo-sorting protein Cab45.
Purpose of the Study:
- To investigate the role of Fam20C in the regulation of Cab45 function.
- To elucidate the mechanism by which Cab45 facilitates the export of its client proteins.
Main Methods:
- In vitro phosphorylation assays to determine if Fam20C phosphorylates Cab45.
- Cellular localization studies to observe the effect of Cab45 phosphorylation on its translocation.
- Analysis of LyzC export in response to altered Cab45 phosphorylation status.
Main Results:
- Fam20C directly phosphorylates the cargo-sorting protein Cab45.
- Phosphorylation of Cab45 mimics its translocation into TGN-derived vesicles.
- This translocation correlates with enhanced export of LyzC, a known Cab45 client protein.
Conclusions:
- Fam20C-mediated phosphorylation is a key regulatory mechanism for Cab45 activity.
- Phosphorylation fine-tunes Cab45 oligomerization, influencing its retention in the TGN and impacting client protein export.
- This study reveals a novel pathway controlling protein secretion via the TGN.
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