Human cancer cells

Jeremy Carlton : Areas of interest

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The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is an evolutionarily-conserved, multi-subunit membrane remodeling complex. Originally identified in yeast for its essential role in the biogenesis of intraluminal vesicles (ILVs) upon a class of endosome called the multivesicular body (MVB), its roles in mammalian cells have been expanded to encompass a number of topologically equivalent membrane remodeling events including release of enveloped retroviruses, completion of the abscission phase of cytokinesis and reformation of the nuclear envelope during mitotic exit (Figure 1).

Cartoon depicting topological equivalence of sites of ESCRT-III activity

Figure 1: A. Cartoon depicting topological equivalence of sites of ESCRT-III activity (*). ESCRT-III localises to membrane stalks and provides an activity allowing resolution of these stalks, leading to separation of membranes that were previously connected by these stalks. This results in release of ILVs at the MVB, release of enveloped retroviruses, separation of daughter cells during cytokinesis and separation of inner and outer nuclear membranes during nuclear envelope reformation. B. Localisation of endogenous ESCRT-III components (CHMP2A) to holes in the reforming nuclear envelope, visualised at the light and electron microscopical level. Bottom panel depicts a volume reconstruction of a correlative light-electron tomography dataset showing CHMP2A localisation to these holes in 3D. 

Using a combination of molecular biology, biochemistry and advanced imaging techniques, we are currently exploring both the mechanics and regulation of ESCRT-III at the nuclear envelope and the nuclear-envelope dependent roles of ESCRT-proteins in regulation of the abscission checkpoint.