Journal
DEVELOPMENTAL CELL
Volume 27, Issue 2, Pages 201-214Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2013.09.009
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Funding
- American Cancer Society [PF-12-062-01-DMC]
- Sam and Nancy Fleming Research Fellowship
- American Cancer Society [PF-12-062-01-DMC]
- Sam and Nancy Fleming Research Fellowship
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The endosomal sorting complexes required for transport (ESCRTs) have emerged as key cellular machinery that drive topologically unique membrane deformation and scission. Understanding how the ESCRT-III polymer interacts with membrane, promoting and/or stabilizing membrane deformation, is an important step in elucidating this sculpting mechanism. Using a combination of genetic and biochemical approaches, both in vivo and in vitro, we identify two essential modules required for ESCRT-III-membrane association: an electrostatic cluster and an N-terminal insertion motif. Mutating either module in yeast causes cargo sorting defects in the MVB pathway. We show that the essential N-terminal insertion motif provides a stable anchor for the ESCRT-III polymer. By replacing this N-terminal motif with well-characterized membrane insertion modules, we demonstrate that the N terminus of Snf7 has been tuned to maintain the topological constraints associated with ESCRT-III-filament-mediated membrane invagination and vesicle formation. Our results provide insights into the spatially unique, ESCRT-III-mediated membrane remodeling.
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