Phosphorylation-Dependent Activation of the ESCRT Function of ALIX in Cytokinetic Abscission and Retroviral Budding

Sun, Sheng; Sun, Le; Zhou, Xi; Wu, Chuanfen; Wang, Ruoning; Lin, Sue Hwa; Kuang, Jian

doi:10.1016/j.devcel.2016.01.001

Cited by 23 publications

(21 citation statements)

References 48 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note, we did not detect any ALIX or syntenin at the plasma membrane in interphase cells, although syndecan-4 is clearly localized there ( Supplementary Movie 4). This suggests that post-translational modifications of either ALIX, syntenin and/or syndecan-4, perhaps via phosphorylations 43,59 regulate the formation of the tripartite complex at the midbody and at the abscission site during cytokinesis.…”

Section: Discussionmentioning

confidence: 99%

The Flemmingsome reveals an ESCRT-to-membrane coupling via ALIX/syntenin/syndecan-4 required for completion of cytokinesis

et al. 2020

View full text Add to dashboard Cite

Cytokinesis requires the constriction of ESCRT-III filaments on the side of the midbody, where abscission occurs. After ESCRT recruitment at the midbody, it is not known how the ESCRT-III machinery localizes to the abscission site. To reveal actors involved in abscission, we obtained the proteome of intact, post-abscission midbodies (Flemmingsome) and identified 489 proteins enriched in this organelle. Among these proteins, we further characterized a plasma membrane-to-ESCRT module composed of the transmembrane proteoglycan syndecan-4, ALIX and syntenin, a protein that bridges ESCRT-III/ALIX to syndecans. The three proteins are highly recruited first at the midbody then at the abscission site, and their depletion delays abscission. Mechanistically, direct interactions between ALIX, syntenin and syndecan-4 are essential for proper enrichment of the ESCRT-III machinery at the abscission site, but not at the midbody. We propose that the ESCRT-III machinery must be physically coupled to a membrane protein at the cytokinetic abscission site for efficient scission, uncovering common requirements in cytokinesis, exosome formation and HIV budding.

show abstract

Section: Discussionmentioning

confidence: 99%

The Flemmingsome reveals an ESCRT-to-membrane coupling via ALIX/syntenin/syndecan-4 required for completion of cytokinesis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To date, the only PTMs known to regulate the structure and function of Alix are ubiquitination and phosphorylation [8,[53][54][55]. Furthermore, our group demonstrated that the binding of OZZ, the substrate binding component of the RING type ubiquitin ligase complex OZZ-E3, changes Alix's conformation and makes the protein accessible for further ubiquitination [8].…”

Section: Alix Interacts With Cd9 and 2bp Affects Their Bindingmentioning

confidence: 95%

Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles

Romancino

Buffa

Caruso

et al. 2018

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

show abstract

“…This arrangement blocks access of CHMP4 and Gag proteins to their binding sites on the Alix surface. Alix activation occurs by several mechanisms including phosphorylation 34 , binding of the membrane adaptors CEP55 35 and ALG-2 34 to the PRR, and subsequent conformational rearrangements and dimerisation 36 , 37 .…”

Section: Introductionmentioning

confidence: 99%

The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function

Gahloth

Heaven

Jowitt

et al. 2017

Sci Rep

View full text Add to dashboard Cite

HD-PTP is a tumour suppressor phosphatase that controls endocytosis, down-regulation of mitogenic receptors and cell migration. Central to its role is the specific recruitment of critical endosomal sorting complexes required for transport (ESCRTs). However, the molecular mechanisms that enable HD-PTP to regulate ESCRT function are unknown. We have characterised the molecular architecture of the entire ESCRT binding region of HD-PTP using small angle X-ray scattering and hydrodynamic analyses. We show that HD-PTP adopts an open and extended conformation, optimal for concomitant interactions with multiple ESCRTs, which contrasts with the compact conformation of the related ESCRT regulator Alix. We demonstrate that the HD-PTP open conformation is functionally competent for binding cellular protein partners. Our analyses rationalise the functional cooperation of HD-PTP with ESCRT-0, ESCRT-I and ESCRT-III and support a model for regulation of ESCRT function by displacement of ESCRT subunits, which is crucial in determining the fate of ubiquitinated cargo.

show abstract

Phosphorylation-Dependent Activation of the ESCRT Function of ALIX in Cytokinetic Abscission and Retroviral Budding

Cited by 23 publications

References 48 publications

The Flemmingsome reveals an ESCRT-to-membrane coupling via ALIX/syntenin/syndecan-4 required for completion of cytokinesis

The Flemmingsome reveals an ESCRT-to-membrane coupling via ALIX/syntenin/syndecan-4 required for completion of cytokinesis

Palmitoylation is a post-translational modification of Alix regulating the membrane organization of exosome-like small extracellular vesicles

The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function

Contact Info

Product

Resources

About