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

Author:

Merigliano ChiaraORCID,Burla RominaORCID,La Torre MattiaORCID,Del Giudice SimonaORCID,Teo HsianglingORCID,Liew Chong WaiORCID,Chojnowski AlexandreORCID,Goh Wah IngORCID,Olmos YolandaORCID,Maccaroni KliziaORCID,Giubettini Maria,Chiolo Irene,Carlton Jeremy G.ORCID,Raimondo Domenico,Vernì FiammettaORCID,Stewart Colin L.ORCID,Rhodes Daniela,Wright Graham D.ORCID,Burke Brian E.ORCID,Saggio IsabellaORCID

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

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