Endocytic vesicle scission by lipid phase boundary forces

Jian Liu, Marko Kaksonen, David G. Drubin, George Oster

Research output: Contribution to journalArticle

Abstract

Endocytosis in budding yeast is thought to occur in several phases. First, the membrane invaginates and then elongates into a tube. A vesicle forms at the end of the tube, eventually pinching off to form a "free" vesicle. Experiments show that actin polymerization is an active participant in the endocytic process, along with a number of membrane-associated proteins. Here we investigate the possible roles of these components in driving vesiculation by constructing a quantitative model of the process beginning at the stage where the membrane invagination has elongated into a tube encased in a sheath of membrane-associated protein. This protein sheath brings about the scission step where the vesicle separates from the tube. When the protein sheath is dynamin, it is commonly assumed that scission is brought about by the constriction of the sheath. Here, we show that an alternative scenario can work as well: The protein sheath acts as a "filter" to effect a phase separation of lipid species. The resulting line tension tends to minimize the interface between the tube region and the vesicle region. Interestingly, large vesicle size can further facilitate the reduction of the interfacial diameter down to a few nanometers, small enough so that thermal fluctuations can fuse the membrane and pinch off the vesicle. To deform the membrane into the tubular vesicle shape, the membrane elastic resistance forces must be balanced by some additional forces that we show can be generated by actin polymerization and/or myosin I. These active forces are shown to be important in successful scission processes as well.

Original languageEnglish (US)
Pages (from-to)10277-10282
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number27
DOIs
StatePublished - Jul 4 2006
Externally publishedYes

Keywords

  • Actin
  • Dynamin
  • Endocytosis
  • Mathematical model
  • Vesiculation

ASJC Scopus subject areas

  • General

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