STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap
| Autor: | Woroniuk, Anna, Porter, Andrew, White, Gavin, Newman, Daniel T., Diamantopoulou, Zoi, Waring, Thomas, Rooney, Claire, Strathdee, Douglas, Marston, Daniel J., Hahn, Klaus M., Sansom, Owen J., Zech, Tobias, Malliri, Angeliki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | 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 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-04404-4 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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