STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.
STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.
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DOI：
10.1038/s41467-018-04404-4
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发表时间：
2018-05-29
影响因子：
16.6
通讯作者：
Malliri A
中科院分区：
文献类型：
--
作者：
Woroniuk A;Porter A;White G;Newman DT;Diamantopoulou Z;Waring T;Rooney C;Strathdee D;Marston DJ;Hahn KM;Sansom OJ;Zech T;Malliri A
核周肌动蛋白帽是一个重要的细胞骨架结构，在前后极化过程中调节核形态和重新定向。调控肌动蛋白帽的机制目前尚不清楚。在这里，我们证明了STEF/TIAM2，一种Rac1选择性鸟嘌呤核苷酸交换因子，定位于核膜，与关键的核周蛋白nesprin2 - 2g和Non-muscle myosin IIB （NMMIIB）共定位，在那里它调节核周Rac1活性。我们发现，STEF耗损减少了顶端核周肌动蛋白索（一种通过将活性Rac1靶向到核膜上而拯救的表型），增加了核高度并损害了核的重新定向。STEF的下调也降低了核周pMLC，降低了核包膜处肌球蛋白产生的张力，表明STEF介导的Rac1活性调节了NMMIIB活性，促进了核周肌动蛋白帽的稳定。最后，STEF的缺失降低了核刚度，降低了taz调控基因的表达。表明由于肌动蛋白帽的破坏，机械传感途径发生改变。核周肌动蛋白帽决定核形态，但目前对其调控知之甚少。在这里，作者发现Rac1 GTPase的激活剂STEF/TIAM2定位于核膜，并有助于核周肌动蛋白和肌球蛋白的张力，这反过来调节肌动蛋白帽。
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.
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影响因子：
50.3
作者：
Diamantopoulou Z;White G;Fadlullah MZH;Dreger M;Pickering K;Maltas J;Ashton G;MacLeod R;Baillie GS;Kouskoff V;Lacaud G;Murray GI;Sansom OJ;Hurlstone AFL;Malliri A
通讯作者：
Malliri A
DOI：
10.1083/jcb.201303055
发表时间：
2013-09-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Alvarez DE;Agaisse H
通讯作者：
Agaisse H
FHOD1与Nesprin-2G的相互作用介导棕褐色线的形成和核运动。
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
4
作者：
Levy JR;Holzbaur EL
通讯作者：
Holzbaur EL
影响因子：
4
作者：
Borrego-Pinto, Joana;Jegou, Thibaud;Gomes, Edgar R.
通讯作者：
Gomes, Edgar R.