ALIX and ESCRT-I/II function as parallel ESCRT-III recruiters in cytokinetic abscission

Christ, Liliane; Wenzel, Eva M.; Liestøl, Knut; Raiborg, Camilla; Campsteijn, Coen; Stenmark, Harald

doi:10.1083/jcb.201507009

Cited by 134 publications

(193 citation statements)

References 83 publications

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“…Among the isolated proteins, we found, as expected, some previously identified interactors, such as CHMP4B, ALIX (ALG2-interacting protein X, also known as programmed cell death 6 interacting protein, PDCD6IP), and three of the four CPC components—Aurora B, Borealin and INCENP—but also some novel partners, including the two components of the centralspindlin complex, KIF23/MKLP1 and MgcRacGAP/RacGAP1 (figure 5 b ; electronic supplementary material, table S1). Centralspindlin is known to play many essential roles during cytokinesis [20,21], including recruiting the protein Cep55 to the midbody [22], which, in turn, has been reported to be necessary for the recruitment of CHMP4C via the intermediate ALIX [23]. Unexpectedly, Cep55 was not identified in our AP-MS purification, although it is possible that this was simply because of MS limitations.…”

Section: Resultsmentioning

confidence: 99%

Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

et al. 2016

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The chromosomal passenger complex (CPC)—composed of Aurora B kinase, Borealin, Survivin and INCENP—surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes in vitro. Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a ‘relay’ mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.

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Section: Resultsmentioning

confidence: 99%

Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

et al. 2016

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“…S7). TSG101 interacts with, and in certain contexts cooperates with ALIX to recruit ESCRT-III machinery (25, 26). Although ALIX co-localized with CHMP4A and other ESCRT components on endolysosomes after damage (Fig.…”

Section: Escrts Respond To Endolysosomal Damagementioning

confidence: 99%

Triggered recruitment of ESCRT machinery promotes endolysosomal repair

Skowyra

Schlesinger

Naismith

et al. 2018

Science

364

500

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Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the Endosomal Sorting Complex Required for Transport (ESCRT) machinery, known to mediate budding and fission on endolysosomes, also plays an essential role in their repair. ESCRTs were rapidly recruited to acutely injured endolysosomes via a pathway requiring calcium and ESCRT-activating factors that was independent of lysophagy. We used live cell imaging to demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts.

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“…On the other hand, various imaging, reconstitution, and overexpression studies had implicated ESCRT-II in cytokinesis 20 and HIV-1 release 17, 21 . It is now clear, based on a study using multiple knockdowns, that ESCRT-II has a direct role in cytokinesis 22 . The chain of interactions involved is identical to that established by structural and reconstitution studies.…”

Section: The Escrt Machinerymentioning

confidence: 99%

“…The first three of these functions can all use the ‘classic’ pathway (ESCRT-I, ESCRT-II, CHMP6), whereas HIV budding and cytokinesis have respective adaptors that can use ALIX to bridge directly to CHMP4 22 . In NE formation, CHMP7 functions as the bridge to CHMP4 108 .…”

Section: Figurementioning

confidence: 99%

Reverse-topology membrane scission by the ESCRT proteins

Schöneberg

Lee

Iwasa

et al. 2016

Nat Rev Mol Cell Biol

371

432

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Preface The narrow membrane necks formed during viral, exosomal, and intra-endosomal budding from membranes, cytokinesis, and related processes have interiors that are contiguous with the cytosol. The severing of these necks involves action from the opposite face of the membrane as compared to the well-characterized coated vesicle pathways, and is referred to as “reverse” or “inverse” topology membrane scission. This process is carried out by the endosomal sorting complexes required for transport (ESCRT) proteins. In particular, the ESCRT-III proteins can form filaments, flat spirals, tubes and conical funnels, which are thought to somehow direct membrane remodeling and scission. Their assembly, and their disassembly by the ATPase VPS4, has been intensively studied, but the mechanism of scission has been elusive. New insights from cryo-electron microscopy and various types of spectroscopy may finally be close to rectifying this situation.

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ALIX and ESCRT-I/II function as parallel ESCRT-III recruiters in cytokinetic abscission

Abstract: Cytokinetic abscission, the final stage of cell division, is mediated by the ESCRT machinery. Here, Christ et al. dissect the regulation of ESCRT-III recruitment and abscission timing and identify an intersection with abscission checkpoint signaling in cells with chromatin bridges.

Cited by 134 publications

References 83 publications

Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis

Triggered recruitment of ESCRT machinery promotes endolysosomal repair

Reverse-topology membrane scission by the ESCRT proteins

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