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

The Journal of cell biology | 2017

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.

Pubmed ID: 28242745 RIS Download

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS077730
  • Agency: NIDA NIH HHS, United States
    Id: R41 DA037622
  • Agency: NIAMS NIH HHS, United States
    Id: T32 AR007612
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR068636
  • Agency: NIAMS NIH HHS, United States
    Id: P30 AR057220
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM099481
  • Agency: NIDA NIH HHS, United States
    Id: R42 DA037622
  • Agency: NINDS NIH HHS, United States
    Id: R21 NS095109

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