title: ALIX and ESCRT-I/II function as parallel ESCRT-III recruiters in cytokinetic abscission.
abstract: Cytokinetic abscission, the final stage of cell division where the two daughter cells are separated, is mediated by the endosomal sorting complex required for transport (ESCRT) machinery. The ESCRT-III subunit CHMP4B is a key effector in abscission, whereas its paralogue, CHMP4C, is a component in the abscission checkpoint that delays abscission until chromatin is cleared from the intercellular bridge. How recruitment of these components is mediated during cytokinesis remains poorly understood, although the ESCRT-binding protein ALIX has been implicated. Here, we show that ESCRT-II and the ESCRT-II-binding ESCRT-III subunit CHMP6 cooperate with ESCRT-I to recruit CHMP4B, with ALIX providing a parallel recruitment arm. In contrast to CHMP4B, we find that recruitment of CHMP4C relies predominantly on ALIX. Accordingly, ALIX depletion leads to furrow regression in cells with chromosome bridges, a phenotype associated with abscission checkpoint signaling failure. Collectively, our work reveals a two-pronged recruitment of ESCRT-III to the cytokinetic bridge and implicates ALIX in abscission checkpoint signaling.
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, N-0379 Oslo, Norway Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway.
authors.forename: Liliane
authors.initials: L
authors.lastname: Christ
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, N-0379 Oslo, Norway Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Wenzel
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, N-0379 Oslo, Norway Department of Informatics, University of Oslo, N-0373 Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, N-0379 Oslo, Norway Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Raiborg
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, N-0379 Oslo, Norway Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway coen.campsteijn@rr-research.no stenmark@ulrik.uio.no.
authors.forename: Coen
authors.initials: C
authors.lastname: Campsteijn
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, N-0379 Oslo, Norway Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway coen.campsteijn@rr-research.no stenmark@ulrik.uio.no.
authors.forename: Harald
authors.initials: H
authors.lastname: Stenmark
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D048749:Cytokinesis; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D014407:Tumor Cells, Cultured
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; C117020:PDCD6IP protein, human