AKTIP interacts with ESCRT I and is needed for the recruitment of ESCRT III subunits to the midbody

To complete mitosis, the bridge that links the two daughter cells needs to be cleaved. This step is carried out by a machinery named “endosomal sorting complex required for transport” (ESCRT). The dissection of this machinery is important in basic biology and for investigating diseases in which cell division is altered. AKTIP, a protein discovered to be associated with telomeres and the nuclear membrane in interphase cells, shares sequence similarities with the ESCRT I component TSG101. This article presents evidence that during mitosis, AKTIP is part of the ESCRT machinery at the midbody.

Specifically, it shows that AKTIP physically interacts with members of the ESCRT machinery and forms a characteristic circular structure at the center of the bridge linking the daughter cells.

Mechanistically, the recruitment of AKTIP is dependent on MKLP1 and independent of CEP55. AKTIP and TSG101 are needed together for the recruitment of the ESCRT III subunit CHMP4B and in parallel for the recruitment of IST1. Alone, the reduction of AKTIP impinges on IST1 and causes multinucleation. Collectively, data in this article reveals that AKTIP is a component of the ESCRT I module and functions in the recruitment of ESCRT III components required for abscission.

Fig 1.  AKTIP localizes as a ring at the dark zone of the midbody.

(A) Confocal immunofluorescence images showing the distribution of AKTIP during mitosis and cytokinesis. HeLa cells were stained with anti-AKTIP (red), anti-α-tubulin (green) and DAPI to visualize DNA (blue). Scale bar, 5μm. (B) Representative 3D-SIM images of cells observed for AKTIP at the midbody in early, mid, late and cut stages. HeLa cells were stained with α-tubulin (green) and AKTIP (red) antibodies. Scale bar, 5μm. (C) Representative fluorescence intensity profile plotted for AKTIP and α-tubulin along the midbody at different stages; early/forming (n = 6), mid (n = 7), late (n = 8), cut (n = 8). (D-E) Representative 3D-SIM images of AKTIP ring (D) and relative measurements (E). Size of AKTIP structure measured in mid (n = 8), late (n = 7) and cut (n = 7) midbodies. Scale bar, 2.5μm. 

Future work hopes to investigate the association of AKTIP with the ESCRT machinery and the impact on cancer which has been described for TSG101 and the ESCRT III subunit CHMP4C.

The full article can be accessed here.

¹Sapienza University Dept. Biology and Biotechnology, Rome, Italy, ²CNR Institute of Molecular Biology and Pathology, Rome, Italy, ³Institute of Structural Biology, Nanyang Technological University, Singapore, ⁴A*STAR, Developmental and Regenerative Biology, ASRL, Agency for Science, Technology and Research, Singapore, ⁵A*STAR, Singapore Nuclear Dynamics and Architecture, Skin ResearchLabs, Agency for Science, Technology and Research, Singapore, ⁶A*STAR Microscopy Platform, Research Support Centre, Agency for Science, Technology and Research, Singapore, ⁷School of Cancer and Pharmaceutical Sciences, King’s College London, London, United Kingdom, ⁸Organelle Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom, ⁹CrestOptics S.p.A., Rome, Italy, ¹⁰University of Southern California, Molecular and Computational Biology Dept., Los Angeles, California, United States of America, ¹¹Sapienza University Dept. Molecular Medicine, Rome, Italy, ¹²Dept. of Physiology National University of Singapore, Singapore, ¹³School of Biological Sciences, Nanyang Technological University, Singapore