A Septin Double Ring Controls the Spatiotemporal Organization of the ESCRT Machinery in Cytokinetic Abscission

Curr Biol. 2019 Jul 8;29(13):2174-2182.e7. doi: 10.1016/j.cub.2019.05.050. Epub 2019 Jun 13.


Abscission is the terminal step of mitosis that physically separates two daughter cells [1, 2]. Abscission requires the endocytic sorting complex required for transport (ESCRT), a molecular machinery of multiple subcomplexes (ESCRT-I/II/III) that promotes membrane remodeling and scission [3-5]. Recruitment of ESCRT-I/II complexes to the midbody of telophase cells initiates ESCRT-III assembly into two rings, which subsequently expand into helices and spirals that narrow down to the incipient site of abscission [6-8]. ESCRT-III assembly is highly dynamic and spatiotemporally ordered, but the underlying mechanisms are poorly understood. Here, we report that, after cleavage furrow closure, septins form a membrane-bound double ring that controls the organization and function of ESCRT-III. The septin double ring demarcates the sites of ESCRT-III assembly into rings and disassembles before ESCRT-III rings expand into helices and spirals. We show that septin 9 (SEPT9) depletion, which abrogates abscission, impairs recruitment of VPS25 (ESCRT-II) and CHMP6 (ESCRT-III). Strikingly, ESCRT-III subunits (CHMP4B and CHMP2A/B) accumulate to the midbody, but they are highly disorganized, failing to form symmetric rings and to expand laterally into the cone-shaped helices and spirals of abscission. We found that SEPT9 interacts directly with the ubiquitin E2 variant (UEV) domain of ESCRT-I protein TSG101 through two N-terminal PTAP motifs, which are required for the recruitment of VPS25 and CHMP6, and the spatial organization of ESCRT-III (CHMP4B and CHMP2B) into functional rings. These results reveal that septins function in the ESCRT-I-ESCRT-II-CHMP6 pathway of ESCRT-III assembly and provide a framework for the spatiotemporal control of the ESCRT machinery of cytokinetic abscission.

Keywords: ESCRT; ESCRT-III; SEPT9; TSG101; abscission; cell division; cytokinesis; endosomal sorting complex required for transport; intercellular bridge; midbody; septins.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cytokinesis*
  • Cytoskeleton / metabolism
  • Dogs
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Madin Darby Canine Kidney Cells
  • Mitosis*
  • Septins / metabolism*


  • Endosomal Sorting Complexes Required for Transport
  • Septins