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STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap
- Source :
- Nature Communications, Vol 9, Iss 1, Pp 1-15 (2018), Nature Communications, Woroniuk, A, Porter, A, White, G, Newman, D, Diamantopoulou, Z, Waring, T, Rooney, C, Strathdee, D, Marston, D J, Hahn, K M, Sansom, O J, Zech, T & Malliri, A 2018, ' STEF/TIAM2 mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap ', Nature Communications, vol. 9, no. 1, 2124 . https://doi.org/10.1038/s41467-018-04404-4
- Publication Year :
- 2018
- Publisher :
- Nature Portfolio, 2018.
-
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.<br />The perinuclear actin cap determines nuclear morphology but its regulation is currently poorly understood. Here, the authors find that an activator of the Rac1 GTPase, STEF/TIAM2, localises to the nuclear envelope and contributes to perinuclear actin and myosin tension, which in turn regulates the actin cap.
- Subjects :
- rac1 GTP-Binding Protein
Actin Capping Proteins/metabolism
Nuclear Envelope
Actin Capping Proteins
Science
Nerve Tissue Proteins/metabolism
Microfilament Proteins/metabolism
Nerve Tissue Proteins
macromolecular substances
Article
Cercopithecus aethiops
Mice
Cell Line, Tumor
Chlorocebus aethiops
Animals
Guanine Nucleotide Exchange Factors
Humans
Transcription Factors/metabolism
lcsh:Science
Nuclear Envelope/metabolism
Nuclear Proteins/metabolism
Guanine Nucleotide Exchange Factors/metabolism
Mice, Knockout
Nonmuscle Myosin Type IIB
Manchester Cancer Research Centre
ResearchInstitutes_Networks_Beacons/mcrc
Microfilament Proteins
Nuclear Proteins
rac1 GTP-Binding Protein/metabolism
Nonmuscle Myosin Type IIB/metabolism
A549 Cells
COS Cells
lcsh:Q
Acyltransferases
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 9
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.pmid.dedup....f1a9c042b2f09eb5875604f0bda003db