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

• Published in: Nature communications Vol. 11; no. 1; p. 1941
• Main Authors: Addi, Cyril, Presle, Adrien, Frémont, Stéphane, Cuvelier, Frédérique, Rocancourt, Murielle, Milin, Florine, Schmutz, Sandrine, Chamot-Rooke, Julia, Douché, Thibaut, Duchateau, Magalie, Giai Gianetto, Quentin, Salles, Audrey, Ménager, Hervé, Matondo, Mariette, Zimmermann, Pascale, Gupta-Rossi, Neetu, Echard, Arnaud
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-04-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/19; 631/80/641; 631/80/641/2090; Abscission; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Membrane - genetics; Cell Membrane - metabolism; Cleavage; Cytokinesis; Depletion; Endosomal Sorting Complexes Required for Transport - genetics; Endosomal Sorting Complexes Required for Transport - metabolism; Endosomes - genetics; Endosomes - metabolism; Filaments; HeLa Cells; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Life Sciences; Membrane proteins; Membranes; multidisciplinary; Organelles - genetics; Organelles - metabolism; Protein Binding; Proteins; Proteoglycans; Proteomes; Proteomics; Science; Science (multidisciplinary); Syndecan; Syndecan-4 - genetics; Syndecan-4 - metabolism; Syntenins - genetics; Syntenins - metabolism; Cell division; Cytokinesis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15205-z

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.
ESCRT filaments drive the final abscission between two daughter cells but how they physically interact with the membrane is unclear. Using proteomics, the authors show that syndecan-4/syntenin/ALIX couples the ESCRT machinery to the abscission site and thus promotes efficient abscission.