Cellular chirality arising from the self-organization of the actin cytoskeleton

Nat Cell Biol. 2015 Apr;17(4):445-57. doi: 10.1038/ncb3137. Epub 2015 Mar 23.

Abstract

Cellular mechanisms underlying the development of left-right asymmetry in tissues and embryos remain obscure. Here, the development of a chiral pattern of actomyosin was revealed by studying actin cytoskeleton self-organization in cells with isotropic circular shape. A radially symmetrical system of actin bundles consisting of α-actinin-enriched radial fibres (RFs) and myosin-IIA-enriched transverse fibres (TFs) evolved spontaneously into the chiral system as a result of the unidirectional tilting of all RFs, which was accompanied by a tangential shift in the retrograde movement of TFs. We showed that myosin-IIA-dependent contractile stresses within TFs drive their movement along RFs, which grow centripetally in a formin-dependent fashion. The handedness of the chiral pattern was shown to be regulated by α-actinin-1. Computational modelling demonstrated that the dynamics of the RF-TF system can explain the pattern transition from radial to chiral. Thus, actin cytoskeleton self-organization provides built-in machinery that potentially allows cells to develop left-right asymmetry.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / physiology*
  • Actinin / metabolism
  • Actomyosin / physiology*
  • Cell Line
  • Cell Shape / physiology*
  • Computer Simulation
  • Humans
  • Muscle Fibers, Skeletal / physiology
  • Nonmuscle Myosin Type IIA / metabolism*
  • RNA Interference
  • RNA, Small Interfering

Substances

  • Actn1 protein, mouse
  • RNA, Small Interfering
  • Actinin
  • Actomyosin
  • Nonmuscle Myosin Type IIA