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J Cell Biol. 2017 Mar 6;216(3):657-674. doi: 10.1083/jcb.201507113. Epub 2017 Feb 27.

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

Author information

1
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
2
Department of Medicine, Columbia University, New York, NY 10032.
3
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
4
Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109.
5
Department of Neurology, University of Michigan, Ann Arbor, MI 48109.
6
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032 gwgl@umn.edu ggg1@columbia.edu.
7
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455 gwgl@umn.edu ggg1@columbia.edu.

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.

PMID:
28242745
PMCID:
PMC5350507
DOI:
10.1083/jcb.201507113
[Indexed for MEDLINE]
Free PMC Article

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