ESCRT-III binding protein MITD1 is involved in cytokinesis and has an unanticipated PLD fold that binds membranes

The endosomal sorting complexes required for transport (ESCRT) proteins have a critical function in abscission, the final separation of the daughter cells during cytokinesis. Here, we describe the structure and function of a previously uncharacterized ESCRT-III interacting protein, MIT-domain contai...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-10, Vol.109 (43), p.17424-17429
Main Authors: Hadders, Michael A, Agromayor, Monica, Obita, Takayuki, Perisic, Olga, Caballe, Anna, Kloc, Magdalena, Lamers, Meindert H, Williams, Roger L, Martin-Serrano, Juan
Format: Article
Language:English
Subjects:
Abscission
binding proteins
Biological Sciences
Cell division
Cells
Crystal structure
Crystallography, X-Ray
Cytokines
Cytokinesis
Cytokinesis - physiology
Dimers
Drug interactions
Endosomal Sorting Complexes Required for Transport - metabolism
Genotype & phenotype
HeLa Cells
Humans
Lipids
Membrane Proteins - chemistry
Membrane Proteins - metabolism
Membrane Proteins - physiology
Microtubule-Associated Proteins - chemistry
Microtubule-Associated Proteins - metabolism
Microtubule-Associated Proteins - physiology
Models, Molecular
phenotype
Phospholipase D - metabolism
Protein Binding
Protein Folding
Proteins
Small interfering RNA
Yeasts
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Summary:The endosomal sorting complexes required for transport (ESCRT) proteins have a critical function in abscission, the final separation of the daughter cells during cytokinesis. Here, we describe the structure and function of a previously uncharacterized ESCRT-III interacting protein, MIT-domain containing protein 1 (MITD1). Crystal structures of MITD1 reveal a dimer, with a microtubule-interacting and trafficking (MIT) domain at the N terminus and a unique, unanticipated phospholipase D-like (PLD) domain at the C terminus that binds membranes. We show that the MIT domain binds to a subset of ESCRT-III subunits and that this interaction mediates MITD1 recruitment to the midbody during cytokinesis. Depletion of MITD1 causes a distinct cytokinetic phenotype consistent with destabilization of the midbody and abscission failure. These results suggest a model whereby MITD1 coordinates the activity of ESCRT-III during abscission with earlier events in the final stages of cell division.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1206839109