Comprehensive analysis of the human ESCRT-III-MIT domain interactome reveals new cofactors for cytokinetic abscission
Year: 2022
Type: article
Abstract: The 12 related human ESCRT-III proteins form filaments that constrict membranes and mediate fission, including during cytokinetic abscission. The C-terminal tails of polymerized ESCRT-III subunits also bind proteins that contain Microtubule-Interacting and Trafficking (MIT) domains. MIT domains can interact with ESCRT-III tails in many different ways to create a complex binding code that is used to recruit essential cofactors to sites of ESCRT activity. Here, we have comprehensively and quantitatively mapped the interactions between all known ESCRT-III tails and 19 recombinant human MIT domains. We measured 228 pairwise interactions, quantified 60 positive interactions, and discovered 18 previously unreported interactions. We also report the crystal structure of the SPASTIN MIT domain in complex with the IST1 C-terminal tail. Three MIT enzymes were studied in detail and shown to: (1) localize to cytokinetic midbody membrane bridges through interactions with their specific ESCRT-III binding partners (SPASTIN-IST1, KATNA1-CHMP3, and CAPN7-IST1), (2) function in abscission (SPASTIN, KATNA1, and CAPN7), and (3) function in the 'NoCut' abscission checkpoint (SPASTIN and CAPN7). Our studies define the human MIT-ESCRT-III interactome, identify new factors and activities required for cytokinetic abscission and its regulation, and provide a platform for analyzing ESCRT-III and MIT cofactor interactions in all ESCRT-mediated processes.
Source: eLife
DOI: 10.7554/elife.77779
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: U.S. Department of Energy, American Cancer Society, University of Utah, Huntsman Cancer Institute, King Saud University, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, Basic Energy Sciences, Biological and Environmental Research, SLAC National Accelerator Laboratory
Awards: G1286251239, G1831385526, G2371548206, G262532246, Role of Calpain-7 in the Abscission Checkpoint, G303061748, G315621713, G3488436650, G3629260272, G4235786860, G4280418065, G4426609375, G4581610328, G534868654, G5570207115, G6550344761, G7283024673, G7941272330, A Synchrotron Radiation Structural Biology Resource, G8925327636, ESCRT and MIT Complexes in Cytokinesis, Cancer Center Support Grant, Dynamic Events at the Nuclear Envelope during Mitosis and Interphase, G911061179, G969889393
OpenAlex ID: W4295888546