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dc.contributor.authorWoroniuk, Anna
dc.contributor.authorPorter, Andrew P
dc.contributor.authorWhite, Gavin R M
dc.contributor.authorNewman, DT
dc.contributor.authorDiamantopoulou, Zoi
dc.contributor.authorWaring, T
dc.contributor.authorRooney, Claire M
dc.contributor.authorStrathdee, D
dc.contributor.authorMarston, D
dc.contributor.authorHahn, K
dc.contributor.authorSansom, O
dc.contributor.authorZech, T
dc.contributor.authorMalliri, Angeliki
dc.date.accessioned2018-07-12T20:28:10Z
dc.date.available2018-07-12T20:28:10Z
dc.date.issued2018-05-29
dc.identifier.citationSTEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. 2018, 9(1): 2124 Nat Communen
dc.identifier.issn2041-1723
dc.identifier.pmid29844364
dc.identifier.doi10.1038/s41467-018-04404-4
dc.identifier.urihttp://hdl.handle.net/10541/621106
dc.description.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.
dc.language.isoenen
dc.rightsArchived with thanks to Nature communicationsen
dc.titleSTEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.en
dc.typeArticleen
dc.contributor.departmentCell Signalling Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, SK10 4TGen
dc.identifier.journalNature Communicationsen
refterms.dateFOA2018-12-17T15:27:44Z
html.description.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.


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