STEF/TIAM2 mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap

Research output: Contribution to journalArticle

  • External authors:
  • Anna Woroniuk
  • Andrew Porter
  • Gavin White
  • Daniel Newman
  • Zoi Diamantopoulou
  • Thomas Waring
  • Claire Rooney
  • Douglas Strathdee
  • Daniel J Marston
  • Klaus M Hahn
  • Owen J. Sansom
  • Tobias Zech

Abstract

The perinuclear actin cap is an important cytoskeletal structure that regulates nuclear morphology and re-orientation during front-rear polarisation. The mechanisms regulating the actin cap are currently poorly understood. Here, we demonstrate that STEF/TIAM2, a Rac1 selective guanine nucleotide exchange factor, localises at the nuclear envelope, co-localising with the key perinuclear proteins Nesprin-2G and Non-muscle myosin IIB (NMMIIB), where it regulates perinuclear Rac1 activity. We show that STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), increases nuclear height and impairs nuclear re-orientation. STEF down-regulation also reduces perinuclear pMLC and decreases myosin-generated tension at the nuclear envelope, suggesting that STEF-mediated Rac1 activity regulates NMMIIB activity to promote stabilisation of the perinuclear actin cap. Finally, STEF depletion decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap.

Bibliographical metadata

Original languageEnglish
JournalNature Communications
Early online date29 May 2018
DOIs
Publication statusPublished - 2018

Related information

Researchers

View all