Essential N-Terminal insertion motif anchors the ESCRT-III filament during MVB vesicle formation

Nicholas J. Buchkovich, William Mike Henne, Shaogeng Tang, Scott D. Emr

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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 invivo and invitro, 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.

Original languageEnglish (US)
Pages (from-to)201-214
Number of pages14
JournalDevelopmental cell
Volume27
Issue number2
DOIs
StatePublished - Oct 28 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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