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.
Funder
Progeria Research Foundation
Sapienza Università di Roma
Associazione Italiana per la Ricerca sul Cancro
Fondazione Italiana per la Ricerca sul Cancro
CIB
Fondazione Adriano Buzzati Traverso
European Molecular Biology Organization
Fondazione Umberto Veronesi
NSF Career
Wellcome Trust Senior Research Fellowship
Cancer Research UK
Medical Research Council
Wellcome Trust
Publisher
Public Library of Science (PLoS)
Subject
Cancer Research,Genetics(clinical),Genetics,Molecular Biology,Ecology, Evolution, Behavior and Systematics
Cited by
15 articles.
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