Basement membrane sliding and targeted adhesion remodels tissue boundaries during uterine-vulval attachment in Caenorhabditis elegans.
Basement membrane sliding and targeted adhesion remodels tissue boundaries during uterine-vulval attachment in Caenorhabditis elegans.
复制标题
DOI：
10.1038/ncb2233
复制
发表时间：
2011-06
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
作者：
在发育和癌症中，基底膜(BM)的大间隙出现在细胞侵袭和组织重塑的位置。尽管从来没有直接在体内进行，但BM的溶解或合成减少被认为是造成这些缺口的原因。利用标志性的光漂白和光学突出层粘连蛋白和IV型胶原，我们发现在线虫子宫-外阴附着过程中，一种新的机制，即BM滑动，导致了子宫-外阴附着期间BM间隙的扩大。激光消融和突变分析表明，内陷的外阴细胞促进了骨髓的移动。此外，RNA干扰和表达筛选确定整合素INA-1/PAT-3和VAB-19是肿瘤抑制因子Kank的同系物，是BM开放的调节因子。两者都集中在BM缝隙边界的外阴细胞内，并阻止移位的BM的扩张。BM滑动后的靶向粘连代表了一种新的机制，可以创建精确的BM破坏，细胞可以使用它来打破间隔边界。
Large gaps in basement membrane (BM) occur at sites of cell invasion and tissue remodelling in development and cancer. Though never followed directly in vivo, BM dissolution or reduced synthesis have been postulated to create these gaps. Using landmark photobleaching and optical highlighting of laminin and type IV collagen, we find that a new mechanism, BM sliding, underlies BM gap enlargement during uterine-vulval attachment in C. elegans. Laser ablation and mutant analysis reveal that the invaginating vulval cells promote BM movement. Further, an RNA interference and expression screen identify the integrin INA-1/PAT-3 and VAB-19, homolog of the tumour suppressor Kank, as regulators of BM opening. Both concentrate within vulval cells at the BM gap boundary and halt expansion of the shifting BM. BM sliding followed by targeted adhesion represents a new mechanism for creating precise BM breaches that can be used by cells to break down compartment boundaries.