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

作者：Hadders Michael A; Agromayor Monica^*; Obita Takayuki; Perisic Olga; Caballe Anna; Kloc Magdalena; Lamers Meindert H; Williams Roger L; Martin Serrano Juan

来源：Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(43): 17424-17429.

DOI：10.1073/pnas.1206839109

• HIV
• multivesicular body
• X-ray crystallography

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.

• 出版日期2012-10-23