학술논문
AKTIP interacts with ESCRT I and is needed for the recruitment of ESCRT III subunits to the midbody.
Document Type
Article
Author
Merigliano, Chiara; Burla, Romina; La Torre, Mattia; Del Giudice, Simona; Teo, Hsiangling; Liew, Chong Wai; Chojnowski, Alexandre; Goh, Wah Ing; Olmos, Yolanda; Maccaroni, Klizia; Giubettini, Maria; Chiolo, Irene; Carlton, Jeremy G.; Raimondo, Domenico; Vernì, Fiammetta; Stewart, Colin L.; Rhodes, Daniela; Wright, Graham D.; Burke, Brian E.; Saggio, Isabella
Source
Subject
*TUMOR susceptibility gene 101
*NUCLEAR membranes
*MACHINE parts
*MITOSIS
*TELOMERES
*CELL division
*CHROMOSOMES
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Language
ISSN
1553-7390
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. Author summary: To complete cell division, 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 factor discovered to be needed for chromosome integrity, shares similarities with a component of the ESCRT machinery named TSG101. Here we present evidence that AKTIP is part of the ESCRT machinery, as TSG101. More specifically, we show 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. We also show that the reduction of AKTIP levels causes defects in the assembly of the ESCRT machinery and in cell division. In future work, it will be interesting to investigate the association of AKTIP with cancer, because in tumorigenesis cell division is altered and since an implication in cancer has been described for TSG101 and other ESCRT factors. [ABSTRACT FROM AUTHOR]