# snz/SNX25 at the crossroad of endocytosis and lipid handling in autophagy

**Authors:** Annie Lauzier, Steve Jean

PMC · DOI: 10.1080/27694127.2022.2047267 · Autophagy Reports · 2022-03-22

## TL;DR

This paper identifies SNX25 as a key regulator of autophagy and lipid handling in both flies and human cells.

## Contribution

The study reveals SNX25's novel role in autophagy and its distinct domains for endocytosis and lipid regulation.

## Key findings

- SNX25 is essential for autophagy in Drosophila and mammalian cells.
- SNX25 regulates VAMP8 endocytosis and lipid handling through separate domains.
- The sorting nexin family's role now includes autophagy regulation.

## Abstract

Macroautophagy/autophagy is coupled to a myriad of intracellular processes, among which vesicular trafficking is an important contributor of membranes and proteins required at various stages, from autophagosome formation to degradation. Hence, understanding how membrane trafficking is coupled to autophagy induction and how cells rewire trafficking upon high autophagic needs is instrumental to our understanding of autophagy. In our recent manuscript, we tested a known class of endosomal sorting regulators, the sorting nexin family, for their involvement in autophagy in Drosophila. We identified snz (snazarus) as an important regulator of autophagy in Drosophila as well as in mammalian cells, by demonstrating a role for the snz human ortholog SNX25 in HeLa cells. Using knockout rescue experiments, we observed that SNX25 loss affects many cellular processes, namely VAMP8 endocytosis and lipid handling. Mutational studies identified separate protein domains involved in these processes. Given the role of this sorting nexin family in lipid droplet regulation, our work expands their requirement to autophagy.

## Linked entities

- **Genes:** snz (snazarus) [NCBI Gene 31704], SNX25 (sorting nexin 25) [NCBI Gene 83891]
- **Proteins:** VAMP8 (vesicle associated membrane protein 8), SNX25 (sorting nexin 25)
- **Species:** Drosophila (taxon 7215)

## Full-text entities

- **Genes:** SNX13 (sorting nexin 13) [NCBI Gene 23161] {aka RGS-PX1}, snz (snazarus) [NCBI Gene 31704] {aka CG1514, DmSNX25, Dmel\CG1514}, VAMP8 (vesicle associated membrane protein 8) [NCBI Gene 8673] {aka EDB, VAMP-8}, SNX14 (sorting nexin 14) [NCBI Gene 57231] {aka RGS-PX2, SCAR20}, VAMP7 (vesicle associated membrane protein 7) [NCBI Gene 6845] {aka SYBL1, TI-VAMP, TIVAMP, VAMP-7}, SNX25 (sorting nexin 25) [NCBI Gene 83891] {aka LRP2BP-AS1, MSTP043, SBBI31}, YKT6 (YKT6 vesicular SNARE protein) [NCBI Gene 10652], SNX19 (sorting nexin 19) [NCBI Gene 399979] {aka CHET8}
- **Chemicals:** phosphatidylserine (MESH:D010718), phosphatidylcholine (MESH:D010713), TM (MESH:D013932), phosphoinositide (MESH:D010716), lipid (MESH:D008055), ETA (MESH:D019856)
- **Species:** Homo sapiens (human, species) [taxon 9606], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Cell lines:** HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11864676/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC11864676/full.md

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Source: https://tomesphere.com/paper/PMC11864676