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

PLoS Genet. 2021 Aug 27;17(8):e1009757. doi: 10.1371/journal.pgen.1009757. eCollection 2021 Aug.

Abstract

To complete mitosis, the bridge that links the two daughter cells needs to be cleaved. This step is carried out by the endosomal sorting complex required for transport (ESCRT) machinery. 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. Here we present evidence that during mitosis AKTIP is part of the ESCRT machinery at the midbody. AKTIP interacts with the ESCRT I subunit VPS28 and forms a circular supra-structure at the midbody, in close proximity with TSG101 and VPS28 and adjacent to the members of the ESCRT III module CHMP2A, CHMP4B and IST1. 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. Our data altogether reveal that AKTIP is a component of the ESCRT I module and functions in the recruitment of ESCRT III components required for abscission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adaptor Proteins, Signal Transducing / physiology
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis Regulatory Proteins / physiology
  • Cell Cycle Proteins / metabolism
  • Cytokinesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • HeLa Cells
  • Humans
  • Mitosis / physiology*
  • Protein Transport
  • Spindle Apparatus / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • AKTIP protein, human
  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • CHMP4B protein, human
  • Cell Cycle Proteins
  • Cep55 protein, human
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Transcription Factors
  • Tsg101 protein
  • VPS28 protein, human