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

Abscission Checkpoint Bodies Reveal a New Facet of Abscission Checkpoint Control

“…Moreover, humans without functional ALIX display microcephaly and kidney defects but are otherwise healthy and can live into their 20s (Khan et al, 2020). We reconcile these observations with our model of the abscission checkpoint in the following ways: 1) Redundant pathways may ensure that abscission (and an abscission checkpoint) takes place in vivo; indeed, a recent report argues that ESCRT proteins, including ALIX, are still recruited to the midbody in the CEP55 knockout mouse (Little et al, 2020), and in cases where ALIX is absent, TSG101 may dominate in driving ESCRT activity (Christ et al, 2016; Karasmanis et al, 2019). 2) It is also possible that tumor-derived cells are more dependent on the ESCRT pathway for abscission than non-cancerous cells, albeit with the exception of the developing brain and kidney.…”

“…CEP55 forms rings on either side of the Flemming body and recruits the early-acting ESCRTs TSG101 (a component of the ESCRT-I complex) and ALIX through a shared binding site (Lee et al, 2008). SEPT9 has also recently been implicated as a second, TSG101/ESCRT-I-specific midbody adaptor (Karasmanis et al, 2019). ALIX and TSG101/ESCRT-I, in turn, ultimately recruit late-acting ESCRT-III factors, including CHMP4B and IST1 through two parallel pathways (Christ et al, 2016).…”

Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions

“…The midbody (MB), a complex protein structure that contains bundles of microtubules at the center of the intercellular bridge, serves as a platform for the assembly of the abscission machinery 2 . The ESCRT-III sub-complex is recruited at both sides of the MB and extends in the form of helical structures to the abscission sites, where it is thought to pinch the plasma membrane [8][9][10][23][24][25][26] . In mammalian cell lines, the adaptor protein Cep55 recruits the ESCRT complex at the MB 6,7 .…”

A Structural View on ESCRT-Mediated Abscission

“…Furthermore, anillin recruits septins, involved in the formation of the constriction sites ( Renshaw et al, 2014 ). The C-terminus of anillin can bind septins, linking anillin and septins to membrane stabilization ( Kinoshita et al, 2002 ; Menon and Gaestel, 2015 ; Karasmanis et al, 2019 ).…”

“…The physical separation of post-mitotic daughter cells is accompanied by a continuous decrease in the diameter of the intercellular bridge at the two opposing sides of the midbody. Initiated by furrow ingression, abscission is the net result of many complex and precisely orchestrated subprocesses ( Agromayor and Martin-Serrano, 2013 ; Henne et al, 2013 ; Mierzwa and Gerlich, 2014 ; Frémont and Echard, 2018 ; Karasmanis et al, 2019 ). According to the vesicle-mediated model, midbody ring-localized secretory vesicles fuse with each other and with the plasma membrane.…”