ESCRTs in membrane sealing

Abstract

The multisubunit endosomal sorting complex required for transport (ESCRT) machinery is a key regulator of cellular membrane dynamics. Initially characterized in the budding yeast Saccharomyces cerevisiae for its involvement in cargo sorting to the vacuole, the yeast lysosome, this protein complex has emerged over the past decade as a driver for diverse membrane remodeling processes. Its pleiotropic functional connection is mirrored in numerous cellular processes, such as cytokinetic abscission during the final step of cell division, nuclear pore quality control, nuclear envelope sealing and repair, plasma membrane repair, vesicle shedding from the plasma membrane, viral budding, and axonal pruning. Common to all the processes regulated by the ESCRT machinery is their assembly on the cytosolic side of the respective membrane to stabilize concave membranes, budding, and scission of narrow membrane necks away from the cytosol. Thus, this machinery has evolved to perform many functions in membrane dynamics, and given its importance, it is not surprising that the dysfunctional ESCRT machinery has been implicated in several diseases. In this mini-review, we summarize the role of ESCRT proteins in membrane deformation specifically during membrane sealing and repair.

The multisubunit endosomal sorting complex required for transport (ESCRT) machinery is a key regulator of cellular membrane dynamics. Initially characterized in the budding yeast Saccharomyces cerevisiae for its involvement in cargo sorting to the vacuole, the yeast lysosome, this protein complex has emerged over the past decade as a driver for diverse membrane remodeling processes. Its pleiotropic functional connection is mirrored in numerous cellular processes, such as cytokinetic abscission during the final step of cell division, nuclear pore quality control, nuclear envelope sealing and repair, plasma membrane repair, vesicle shedding from the plasma membrane, viral budding, and axonal pruning. Common to all the processes regulated by the ESCRT machinery is their assembly on the cytosolic side of the respective membrane to stabilize concave membranes, budding, and scission of narrow membrane necks away from the cytosol. Thus, this machinery has evolved to perform many functions in membrane dynamics, and given its importance, it is not surprising that the dysfunctional ESCRT machinery has been implicated in several diseases. In this mini-review, we summarize the role of ESCRT proteins in membrane deformation specifically during membrane sealing and repair.