TY - JOUR
T1 - Cellular chirality arising from the self-organization of the actin cytoskeleton
AU - Tee, Yee Han
AU - Shemesh, Tom
AU - Thiagarajan, Visalatchi
AU - Hariadi, Rizal Fajar
AU - Anderson, Karen L.
AU - Page, Christopher
AU - Volkmann, Niels
AU - Hanein, Dorit
AU - Sivaramakrishnan, Sivaraj
AU - Kozlov, Michael M.
AU - Bershadsky, Alexander D.
N1 - Funding Information:
We thank P. Lappalainen for discussion, S. Hanks, B. M. Jockush, I. Kaverina, C. Otey, P. Roca-Cusachs, M. J. Schell and R. Wedlich-Soldner for providing reagents, C. Lu for writing the custom script for velocities measurement, Z. Z. Lieu for help in the knockdown study, S. Wolf for expert help in paper editing, the microscopy core facility at the Mechanobiology Institute for technical help and Sanford Burnham Medical Research Institute for electron microscopy work. This research has been supported by the National Research Foundation Singapore, Ministry of Education of Singapore, Grant R-714-006-006-271, and administrated by the National University of Singapore. K.L.A. and D.H. were supported by National Institutes of Health (NIH) grant P01-GM098412. C.P. and N.V. were supported by NIH grant P01-GM066311. M.M.K. was supported by the Israel Science Foundation (grant No.758/11) and the Marie Curie network Virus Entry, and holds the Joseph Klafter Chair in Biophysics. M.M.K. thanks the Mechanobiology Institute, National University of Singapore, for hospitality. A.D.B. holds the Joseph Moss Professorial Chair in Biomedical Research at the Weizmann Institute and is a Visiting Professor at the National University of Singapore and acknowledges support from the Israel Science Foundation (grant No. 956/10).
Publisher Copyright:
© 2015 Macmillan Publishers Limited.
PY - 2015/4/30
Y1 - 2015/4/30
N2 - 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.
AB - 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.
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U2 - 10.1038/ncb3137
DO - 10.1038/ncb3137
M3 - Article
C2 - 25799062
AN - SCOPUS:84925945544
SN - 1465-7392
VL - 17
SP - 445
EP - 457
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 4
ER -