Vps68 cooperates with ESCRT-III in intraluminal vesicle formation

Alsleben, Sören; Kölling, Ralf

doi:10.1242/jcs.259743

Cited by 5 publications

(14 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The short-lived endocytic cargo protein Ste6 is transported to the yeast vacuole for degradation via the multivesicular body pathway (Kölling and Hollenberg, 1994). As described before, Ste6 is stabilized in the ∆vps68 mutant (Alsleben and Kölling, 2022). We now took a closer look at the kinetics of Ste6 degradation using a gal-depletion experiment.…”

Section: Kinetics Of Ste6 Turnover In the Vps68 Deletion Mutantmentioning

confidence: 96%

“…In our previous study we identified Vps68 as an interaction partner of ESCRT-III (Alsleben and Kölling, 2022). Since Vps68 forms a complex with Vps55 (Schluter et al, 2008), we were interested to see, if Vps55 as well associates with ESCRT-III.…”

Section: Vps55 Interacts With Escrt-iiimentioning

confidence: 99%

“…Recently, we identified Vps68 as an interaction partner of Mos10 (Alsleben and Kölling, 2022). Vps68 forms a complex with Vps55, whose role in endocytic trafficking has been studied previously (Belgareh-Touze et al, 2002; Huh et al, 2003; Schluter et al, 2008; Suzuki et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Both proteins have a similar structure basically consisting of four transmembrane spanning segments (TMDs). Deletion of VPS55 and/or VPS68 has only a moderate effect on the degradation of endocytic cargo proteins (Alsleben and Kölling, 2022; Schluter et al, 2008). But here, we identified another factor ( TMS1 ), whose deletion leads to a complete block in the degradation of an endocytic cargo protein in combination with the VPS68 deletion.…”

Section: Introductionmentioning

confidence: 99%

“…We have been especially interested in the ESCRT-III associated protein Mos10 (also known as Vps60) (KRANZ et al 2001). Recent evidence suggests that Mos10 forms an alternative ESCRT-III complex independent of the canonical Snf7 containing complex (ALSLEBEN AND KÖLLING 2022;PFITZNER et al 2023). Both complexes appear to be involved in the formation of intraluminal vesicles (ILVs) during multivesicular body (MVB) formation in the endocytic pathway (PFITZNER et al 2023).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Link between lipid remodeling and ESCRT-III function in multivesicular body formation

Kölling

2023

Preprint

Self Cite

View full text Add to dashboard Cite

Despite a tremendous amount of work, it is still unclear how the endosomal sorting complex required for transport (ESCRT)-III complex acts in membrane remodeling and abscission. Here we present evidence that a change in membrane composition is connected to ESCRT-III function during multivesicular body (MVB) formation. The central observation was a strong synergistic effect of two mutations on the turnover of an endocytic cargo protein. One mutation deletes Tms1, a yeast SERINC homologue. Human SERINC3 and SERINC5 are HIV-1 restriction factors and have been shown to act as scramblases, flipping phospholipids between membrane leaflets. The other mutation deletes the Vps68 subunit of the Vps55/Vps68 complex, which loosely resembles Tms1 in its overall structure. The strong synergistic effect suggests that Tms1 and Vps55/Vps68 perform a similar function. Since we could also show that Vps55 physically interacts with ESCRT-III, we propose that a scramblase is recruited to ESCRT-III and prepares the membrane for intraluminal vesicles formation at MVBs.SummaryIt is still unclear how ESCRT-III acts on membranes. Here evidence is presented that ESCRT-III recruits a scramblase to the site of intraluminal vesicle formation at late endosomes indicating that a change in membrane composition is crucial for MVB formation.

show abstract

Section: Kinetics Of Ste6 Turnover In the Vps68 Deletion Mutantmentioning

confidence: 96%

Section: Vps55 Interacts With Escrt-iiimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Link between lipid remodeling and ESCRT-III function in multivesicular body formation

Kölling

2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Vps60 initiates alternative ESCRT-III filaments

Pfitzner,

Zivkovic,

Bernat-Silvestre

et al. 2023

Journal of Cell Biology

View full text Add to dashboard Cite

Endosomal sorting complex required for transport-III (ESCRT-III) participates in essential cellular functions, from cell division to endosome maturation. The remarkable increase of its subunit diversity through evolution may have enabled the acquisition of novel functions. Here, we characterize a novel ESCRT-III copolymer initiated by Vps60. Membrane-bound Vps60 polymers recruit Vps2, Vps24, Did2, and Ist1, as previously shown for Snf7. Snf7- and Vps60-based filaments can coexist on membranes without interacting as their polymerization and recruitment of downstream subunits remain spatially and biochemically separated. In fibroblasts, Vps60/CHMP5 and Snf7/CHMP4 are both recruited during endosomal functions and cytokinesis, but their localization is segregated and their recruitment dynamics are different. Contrary to Snf7/CHMP4, Vps60/CHMP5 is not recruited during nuclear envelope reformation. Taken together, our results show that Vps60 and Snf7 form functionally distinct ESCRT-III polymers, supporting the notion that diversification of ESCRT-III subunits through evolution is linked to the acquisition of new cellular functions.

show abstract

Interaction between ESCRT-III proteins and the yeast SERINC homolog Tms1

Kölling

2024

Genetics

View full text Add to dashboard Cite

The endosomal sorting complex required for transport (ESCRT)-III is involved in membrane remodeling and abscission during intraluminal vesicle (ILV) formation at endosomes. Our data now suggest that ESCRT-III function could be connected to lipid remodeling of the endosomal membrane. This notion is based on our finding that ESCRT-III proteins bind to the yeast serine incorporator (SERINC) homolog Tms1. Human SERINC3 and SERINC5 are HIV-1 restriction factors and have been shown to act as scramblases, flipping phospholipids between membrane leaflets. Due to the extraordinarily high sequence conservation between Tms1 and human SERINCs, it is likely that Tms1 is also a scramblase. While deletion of TMS1 had only a moderate effect on the sorting of multivesicular body (MVB) cargo proteins, the simultaneous deletion of a component of the Vps55/Vps68 complex led to a strong synergistic phenotype. This pronounced synergism suggests that Tms1 and Vps55/Vps68 perform a parallel function at endosomes. Vps55/Vps68 loosely resembles Tms1 in its overall structure. Thus, it is possible that Vps55/Vps68 is also a scramblase. Since both Vps55 and Tms1 physically interact with ESCRT-III proteins, we propose that the recruitment of a scramblase plays a crucial role in ESCRT-III-dependent membrane remodeling at endosomes.

show abstract

Vps68 cooperates with ESCRT-III in intraluminal vesicle formation

Cited by 5 publications

References 44 publications

Link between lipid remodeling and ESCRT-III function in multivesicular body formation

Link between lipid remodeling and ESCRT-III function in multivesicular body formation

Vps60 initiates alternative ESCRT-III filaments

Interaction between ESCRT-III proteins and the yeast SERINC homolog Tms1

Contact Info

Product

Resources

About