Finding independent roles for different cellular ESCRTs

2010

Challenge

The cellular cleanup machinery includes a series of molecules called Endosomal Sorting Complex Required for Transport (ESCRTs) whose job it is to identify and flag proteins destined for liposomal processing and removal from the cell. How the ESCRT complexes assemble and function at a mechanistic level was poorly understood. 

Advance

IRP researchers led by Dr. Jim Hurley reconstituted the ESCRT process and destruction of target proteins within the cell using a system of purified proteins and synthetic lipid vesicles. The team visualized the reaction using fluorescent ESCRT complexes and showed that each ESCRT plays a distinct and different role in the process. Their observations explained the ways ESCRTs direct protein flagging and transport to the cellular membrane, as well as the actual excision of the protein from within the structure—all without themselves being consumed within the reaction. 

Impact

This study was one of the most complex reconstitutions of a membrane biology process ever undertaken, involving a total of 15 different proteins. It culminated in the discovery of the ESCRT bud neck assembly, which is now a target of further investigation.

Publications

Wollert, T. and Hurley, J. H. (2010). Molecular Mechanism of Multivesicular Body Biogenesis by ESCRT Complexes. Nature. 464(7290), 864-869.