Laboratory of Molecular Biology, Medical Research Council, Cambridge CB2 0QH, United Kingdom.
Proc Natl Acad Sci U S A. 2012 Oct 23;109(43):17424-9. doi: 10.1073/pnas.1206839109. Epub 2012 Oct 8.
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.
内体分选复合物需要运输（ESCRT）蛋白在胞质分裂的末期分离子细胞中具有关键作用。在这里，我们描述了一个以前未被表征的 ESCRT-III 相互作用蛋白，MIT 结构域包含蛋白 1（MITD1）的结构和功能。MITD1 的晶体结构揭示了一个二聚体，其 N 端具有微管相互作用和运输（MIT）结构域，C 端具有独特的、出乎意料的磷脂酶 D 样（PLD）结构域，该结构域结合膜。我们表明，MIT 结构域与一组 ESCRT-III 亚基结合，这种相互作用介导了胞质分裂过程中 MITD1 向中体的募集。MITD1 的耗竭会导致明显的胞质分裂表型，这与中体的不稳定和胞质分裂失败一致。这些结果表明了一个模型，即 MITD1 在胞质分裂过程中与 ESCRT-III 的活性相协调，与细胞分裂的最后阶段的早期事件相协调。
