Forces drive basement membrane invasion in Caenorhabditis elegans.
Forces drive basement membrane invasion in Caenorhabditis elegans.
复制标题
DOI：
10.1073/pnas.1808760115
复制
发表时间：
2018-11-06
影响因子：
11.1
通讯作者：
Plastino J
中科院分区：
文献类型：
--
作者：
Cáceres R;Bojanala N;Kelley LC;Dreier J;Manzi J;Di Federico F;Chi Q;Risler T;Testa I;Sherwood DR;Plastino J
基底膜是一种特殊的片状细胞外基质，可分隔组织区室。通过基底膜屏障侵入细胞是许多正常和病理过程的一个关键方面，包括器官发育和癌细胞转移。侵入性突起富含肌动蛋白，这是一种细胞骨架生物聚合物，其自组装可以产生力并重塑细胞外基质。然而，在侵入性突出中，肌动蛋白被认为具有支架和运输功能，其机械作用尚未被探索。在这里，我们表明秀丽隐杆线虫中的入侵细胞通过肌动蛋白组装施加力来突破基底膜，而力的产生是入侵的关键特征之一。在侵袭过程中，细胞突破具有富含肌动蛋白的突起的基底膜（BM）屏障。然而，目前尚不清楚肌动蛋白聚合是否会施加推力来帮助突破 BM，或者肌动蛋白丝是否作为靶向侵入性机械的支架发挥被动作用。在这里，利用秀丽隐杆线虫锚细胞（AC）入侵的发育事件，我们观察到AC在入侵之前使BM和底层组织变形，施加数十纳牛顿范围的力。变形是由 Arp2/3 复合物及其激活剂成核的肌动蛋白聚合驱动的，而福尔明和交联剂是可有可无的。肌动蛋白调节因子丧失时的侵袭延迟不是由 AC 极性、运输或分泌缺陷引起的，因为即使肌动蛋白减少且侵袭被破坏，适当的标记也正确定位在 AC 中。这项研究表明，整体力的产生是入侵细胞用来促进线虫 BM 破坏的主要工具之一。
Basement membrane is a particular kind of sheet-like extracellular matrix that separates tissue compartments. Invasion of cells through basement membrane barriers is a key aspect of many normal and pathological processes, including organ development and cancer cell metastasis. Invasive protrusions are rich in actin, a cytoskeletal biopolymer, the self-assembly of which can produce force and remodel extracellular matrix. However, in the invasive protrusion, actin has been attributed a function in scaffolding and trafficking, and its mechanical role has not been explored. Here we show that invading cells in C. elegans apply forces via actin assembly to break through basement membrane, and that force production is one of the key features of invasion. During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion in Caenorhabditis elegans, we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption in C. elegans.
登录
查看更多内容
影响因子：
11.8
作者：
Naegeli KM;Hastie E;Garde A;Wang Z;Keeley DP;Gordon KL;Pani AM;Kelley LC;Morrissey MA;Chi Q;Goldstein B;Sherwood DR
通讯作者：
Sherwood DR
影响因子：
6.6
作者：
Beaty, Brian T.;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
11.8
作者：
Matus DQ;Lohmer LL;Kelley LC;Schindler AJ;Kohrman AQ;Barkoulas M;Zhang W;Chi Q;Sherwood DR
通讯作者：
Sherwood DR
影响因子：
64.5
作者：
Sherwood, DR;Butler, JA;Sternberg, PW
通讯作者：
Sternberg, PW
影响因子：
9.8
作者：
Dayel, Mark J.;Akin, Orkun;Mullins, R. Dyche
通讯作者：
Mullins, R. Dyche