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

Cyril Addi, Adrien Presle, Stéphane Frémont, Frédérique Cuvelier, Murielle Rocancourt, Florine Milin, Sandrine Schmutz, Julia Chamot-Rooke, Thibaut Douché, Magalie Duchateau, Quentin Giai Gianetto, Audrey Salles, Hervé Ménager, Mariette Matondo, Pascale Zimmermann, Neetu Gupta-Rossi and Arnaud Echard ()
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Cyril Addi: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS
Adrien Presle: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS
Stéphane Frémont: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS
Frédérique Cuvelier: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS
Murielle Rocancourt: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS
Florine Milin: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS
Sandrine Schmutz: Institut Pasteur, UTechS CB
Julia Chamot-Rooke: Institut Pasteur, Mass Spectrometry for Biology Unit, C2RT, USR 2000, CNRS
Thibaut Douché: Institut Pasteur, Proteomics Platform, Mass Spectrometry for Biology, C2RT, USR 2000, CNRS
Magalie Duchateau: Institut Pasteur, Proteomics Platform, Mass Spectrometry for Biology, C2RT, USR 2000, CNRS
Quentin Giai Gianetto: Institut Pasteur, Proteomics Platform, Mass Spectrometry for Biology, C2RT, USR 2000, CNRS
Audrey Salles: UTechS Photonic BioImaging PBI (Imagopole), Centre de Recherche et de Ressources Technologiques C2RT, Institut Pasteur
Hervé Ménager: Hub de Bioinformatique et Biostatistique – Département Biologie Computationnelle, Institut Pasteur, USR 3756 CNRS
Mariette Matondo: Institut Pasteur, Proteomics Platform, Mass Spectrometry for Biology, C2RT, USR 2000, CNRS
Pascale Zimmermann: Centre de Recherche en Cancérologie de Marseille (CRCM), Equipe labellisée Ligue 2018, Aix-Marseille Université, Inserm, CNRS, Institut Paoli Calmettes
Neetu Gupta-Rossi: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS
Arnaud Echard: Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-15205-z

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