STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.
Porter, Andrew P
White, Gavin R M
Rooney, Claire M
AffiliationCell Signalling Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, SK10 4TG
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AbstractThe 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.
CitationSTEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. 2018, 9(1): 2124 Nat Commun
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- TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement.
- Authors: Saunders CA, Harris NJ, Willey PT, Woolums BM, Wang Y, McQuown AJ, Schoenhofen A, Worman HJ, Dauer WT, Gundersen GG, Luxton GW
- Issue date: 2017 Mar 6
- Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts.
- Authors: Chang W, Folker ES, Worman HJ, Gundersen GG
- Issue date: 2013 Dec
- Identification of the stef gene that encodes a novel guanine nucleotide exchange factor specific for Rac1.
- Authors: Hoshino M, Sone M, Fukata M, Kuroda S, Kaibuchi K, Nabeshima Y, Hama C
- Issue date: 1999 Jun 18