Department of Biology, Duke University, Science Drive, Box 90388, Durham, North Carolina 27708, USA.
Nat Cell Biol. 2011 Jun;13(6):641-51. doi: 10.1038/ncb2233. Epub 2011 May 15.
Large gaps in basement membrane occur at sites of cell invasion and tissue remodelling in development and cancer. Though never followed directly in vivo, basement membrane 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, basement membrane sliding, underlies basement membrane gap enlargement during uterine-vulval attachment in Caenorhabditis elegans. Laser ablation and mutant analysis reveal that the invaginating vulval cells promote basement membrane movement. Further, an RNA interference and expression screen identifies the integrin INA-1/PAT-3 and VAB-19, homologue of the tumour suppressor Kank, as regulators of basement membrane opening. Both concentrate within vulval cells at the basement membrane gap boundary and halt expansion of the shifting basement membrane. Basement membrane sliding followed by targeted adhesion represents a new mechanism for creating precise basement membrane breaches that can be used by cells to break down compartment boundaries.
在发育和癌症过程中，细胞侵袭和组织重塑部位的基底层膜会出现大的间隙。尽管从未直接在体内进行跟踪，但据推测基底层膜的溶解或减少合成会产生这些间隙。通过使用地标光漂白和层粘连蛋白和 IV 型胶原的光学突出显示，我们发现了一种新的机制，即基底层膜滑动，它是秀丽隐杆线虫子宫-外阴附着过程中基底层膜间隙扩大的基础。激光消融和突变分析表明，内陷的外阴细胞促进基底层膜运动。此外，RNA 干扰和表达筛选鉴定出整合素 INA-1/PAT-3 和 VAB-19，肿瘤抑制因子 Kank 的同源物，是基底层膜开口的调节剂。它们都在基底层膜间隙边界处的外阴细胞内浓缩，并阻止了移动基底层膜的扩展。随后的靶向粘附的基底层膜滑动代表了一种新的机制，可以用来创建精确的基底层膜破裂，使细胞能够打破隔室边界。
