RNA localization in confined cells depends on cellular mechanical activity and contributes to confined migration.
RNA localization in confined cells depends on cellular mechanical activity and contributes to confined migration.
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DOI：
10.1016/j.isci.2022.103845
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发表时间：
2022-02-18
期刊：
影响因子：
5.8
通讯作者：
Stroka KM
中科院分区：
文献类型：
--
作者：
Moriarty RA;Mili S;Stroka KM
癌细胞在转移过程中受到机械约束，因此可以改变它们的迁移机制。大量mRNAs定位于细胞突起，导致细胞极化和迁移，并受能结合RNA和/或细胞骨架元件的蛋白质控制，如结肠腺瘤性息肉病(APC)。在这里，我们证明了APC依赖的RNA在受限微通道内的细胞中的外围定位与细胞类型有关。这种不同的表型由去酪氨酸化的微管蛋白网络的水平决定。我们表明，这个网络是由机械活性调节的，具有机械敏感离子通道和肌球蛋白II活性增加的细胞直接对Rab13 APC依赖的RNA进行外围定位。通过Rab13 RNA的特定错误定位，我们表明外周RNA的定位有助于限制细胞的迁移。我们的结果表明，细胞的机械活动决定了它外围靶向RNA并利用它们在限制条件下移动的能力。限制中依赖APC的RNA的外周定位取决于细胞类型RNA在受限细胞中的定位受细胞的机械性控制RNA定位表型受降解的微管蛋白网络的影响外周RNA的积累对受限细胞的迁移具有重要作用生物科学；生物工程；细胞生物学；生物物理学
Cancer cells experience mechanical confining forces during metastasis and, consequently, can alter their migratory mechanisms. Localization of numerous mRNAs to cell protrusions contributes to cell polarization and migration and is controlled by proteins that can bind RNA and/or cytoskeletal elements, such as the adenomatous polyposis coli (APC). Here, we demonstrate that peripheral localization of APC-dependent RNAs in cells within confined microchannels is cell type dependent. This varying phenotype is determined by the levels of a detyrosinated tubulin network. We show that this network is regulated by mechanoactivity and that cells with mechanosensitive ion channels and increased myosin II activity direct peripheral localization of the RAB13 APC-dependent RNA. Through specific mislocalization of the RAB13 RNA, we show that peripheral RNA localization contributes to confined cell migration. Our results indicate that a cell’s mechanical activity determines its ability to peripherally target RNAs and utilize them for movement in confinement. Peripheral localization of APC-dependent RNAs in confinement depends on cell type RNA localization in confined cells is controlled by the mechanoactivity of cells RNA localization phenotype is influenced by the detyrosinated tubulin network Peripheral RNA accumulation functionally contributes to confined cell migration Biological sciences; Bioengineering; Cell biology; Biophysics
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影响因子：
11.8
作者：
Dermit M;Dodel M;Lee FCY;Azman MS;Schwenzer H;Jones JL;Blagden SP;Ule J;Mardakheh FK
通讯作者：
Mardakheh FK
影响因子：
2.9
作者：
Lessey EC;Guilluy C;Burridge K
通讯作者：
Burridge K
DOI：
10.1126/science.aba2894
发表时间：
2020-10-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lomakin AJ;Cattin CJ;Cuvelier D;Alraies Z;Molina M;Nader GPF;Srivastava N;Sáez PJ;Garcia-Arcos JM;Zhitnyak IY;Bhargava A;Driscoll MK;Welf ES;Fiolka R;Petrie RJ;De Silva NS;González-Granado JM;Manel N;Lennon-Duménil AM;Müller DJ;Piel M
通讯作者：
Piel M
影响因子：
4.8
作者：
Balzer, Eric M.;Tong, Ziqiu;Konstantopoulos, Konstantinos
通讯作者：
Konstantopoulos, Konstantinos
影响因子：
64.8
作者：
Chicurel, ME;Singer, RH;Ingber, DE
通讯作者：
Ingber, DE