Can filament treadmilling alone account for the F-actin turnover in lamellipodia?

Takushi Miyoshi, Naoki Watanabe

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Actin forms a polarized filament that grows at the barbed end and shrinks at the pointed end. This phenomenon known as "treadmilling" is believed to govern actin filament turnover. However, in the cell, whether actin turnover proceeds by treadmilling or by other reactions, including filament severing, is a debatable issue. Our previous fluorescence single-molecule speckle (SiMS) analysis has yielded data about the lifetime distribution of F-actin, the uncapping kinetics of both the barbed and pointed ends of the filaments and the elongation rate of the barbed end in lamellipodia. Given these parameters, we estimated the rate of disassembly of the pointed end required to achieve the observed fast actin turnover under the assumption of exclusive filament treadmilling. We derived a method for calculating the lifetime of an individual F-actin subunit at a given position in the Arp2/3 complex-nucleated filament. Extension of this derivation revealed that in the absence of disassembly in the other portions of the filaments, at least 100-fold acceleration of the in vitro pointed end disassembly rate is required to achieve observed F-actin lifetime distribution in lamellipodia. It is, therefore, unlikely that treadmilling solely accounts for the actin filament turnover in vivo. Accumulating evidence obtained by SiMS analysis implies a non-treadmilling actin turnover mechanism in which a substantial amount of F-actin might disassemble near the barbed end of the filament.

Original languageEnglish
Pages (from-to)179-190
Number of pages12
JournalCytoskeleton
Volume70
Issue number4
DOIs
Publication statusPublished - 2013 Apr
Externally publishedYes

Keywords

  • Actin filament turnover
  • Cofilin
  • Filament severing
  • Lamellipodia
  • Single-molecule speckle (SiMS) microscopy

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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