TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement

Cosmo A. Saunders, Nathan J. Harris, Patrick T. Willey, Brian M. Woolums, Yuexia Wang, Alex J. McQuown, Amy Schoenhofen, Howard J. Worman, William T. Dauer, Gregg G. Gundersen, G. W.Gant Luxton

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The nucleus is positioned toward the rear of most migratory cells. In fibroblasts and myoblasts polarizing for migration, retrograde actin flow moves the nucleus rearward, resulting in the orientation of the centrosome in the direction of migration. In this study, we report that the nuclear envelope-localized AAA+ (ATPase associated with various cellular activities) torsinA (TA) and its activator, the inner nuclear membrane protein lamina-associated polypeptide 1 (LAP1), are required for rearward nuclear movement during centrosome orientation in migrating fibroblasts. Both TA and LAP1 contributed to the assembly of transmembrane actin-associated nuclear (TAN) lines, which couple the nucleus to dorsal perinuclear actin cables undergoing retrograde flow. In addition, TA localized to TAN lines and was necessary for the proper mobility of EGFP-mini-nesprin-2G, a functional TAN line reporter construct, within the nuclear envelope. Furthermore, TA and LAP1 were indispensable for the retrograde flow of dorsal perinuclear actin cables, supporting the recently proposed function for the nucleus in spatially organizing actin flow and cytoplasmic polarity. Collectively, these results identify TA as a key regulator of actin-dependent rearward nuclear movement during centrosome orientation.

Original languageEnglish (US)
Pages (from-to)657-674
Number of pages18
JournalThe Journal of cell biology
Volume216
Issue number3
DOIs
StatePublished - Mar 6 2017
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement'. Together they form a unique fingerprint.

  • Cite this

    Saunders, C. A., Harris, N. J., Willey, P. T., Woolums, B. M., Wang, Y., McQuown, A. J., Schoenhofen, A., Worman, H. J., Dauer, W. T., Gundersen, G. G., & Luxton, G. W. G. (2017). TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement. The Journal of cell biology, 216(3), 657-674. https://doi.org/10.1083/jcb.201507113