PgmNr Y527: SNX-BAR proteins contribute to autophagy via trafficking of lipids required for autophagosome-vacuole fusion.

Authors:
R. J. Chi 1 ; M. Ma 2 ; S. Kumar 2 ; J. Wang 2 ; M. Babst 3 ; C. Burd 2


Institutes
1) University of North Carolina at Charlotte, Charlotte, North Carolina; 2) Yale School of Medicine New Haven, Connecticut; 3) University of Utah, Salt Lake City, Utah.


Keyword: Protein Sorting and Turnover

Abstract:

The yeast SNX4 family of sorting nexins containing a BAR domain (SNX-BARs), Snx4/Atg24, Snx41, and Snx42/Atg20, are components of endocytic recycling and autophagy trafficking pathways.  We show that these proteins possess membrane remodeling activity in vitro and coat endosome-derived transport carriers in vivo.  Endosomes decorated by Snx4 proteins are also decorated with retromer SNX-BARs, but each SNX-BAR coats a distinct carrier that buds from the endosome, indicating that, in contrast to current models, the SNX4 and retromer pathways originate from a common endosome.  Cells lacking Snx4 family proteins display a modest deficiency in autophagy that is severely exacerbated when mitochondrial phosphatidylethanolamine synthesis is ablated.  Under these conditions, the lipid content of endosome-related organelles is perturbed and autophagosomes accumulate within the cytoplasm as a result of deficient fusion with the lysosome-like vacuole. SNARE-mediated autophagosome-vacuole fusion is restored by increasing phosphatidylethanolamine biosynthesis via alternative pathways, revealing a role for sorting nexins in controlling local pools of glycerophospholipids.



Yeast Database Genetic Index
1. gene symbol: Snx4
2. gene symbol: Snx41
3. gene symbol: Snx42
4. gene symbol: Atg8
5. gene symbol: Vps5
6. gene symbol: Vps17
7. gene symbol: Vps26
8. gene symbol: Vps29
9. gene symbol: Vps35
10. gene symbol: Vps1