Department of Developmental Biology, European Molecular Biology Laboratory Heidelberg, Meyerhofstrasse 1, Heidelberg 69117, Germany.
Nat Commun. 2013;4:2244. doi: 10.1038/ncomms3244.
During morphogenesis, remodelling of cell shape requires the expansion or contraction of plasma membrane domains. Here we identify a mechanism underlying the restructuring of the apical surface during epithelial morphogenesis in Drosophila. We show that the retraction of villous protrusions and subsequent apical plasma membrane flattening is an endocytosis-driven morphogenetic process. Quantitation of endogenously tagged GFP::Rab5 dynamics reveals a massive increase in apical endocytosis that correlates with changes in apical morphology. This increase is accompanied by the formation of tubular plasma membrane invaginations that serve as platforms for the de novo generation of Rab5-positive endosomes. We identify the Rab5-effector Rabankyrin-5 as a regulator of this pathway and demonstrate that blocking dynamin activity results in the complete inhibition of tubular endocytosis, in the disappearance of Rab5 endosomes, and in the inhibition of surface flattening. These data collectively demonstrate a requirement for endocytosis in morphogenetic remodelling during epithelial development.
在形态发生过程中,细胞形状的重塑需要细胞质膜域的扩展或收缩。在这里,我们确定了果蝇上皮形态发生过程中顶端表面重构的机制。我们表明,绒毛状突起的缩回和随后的顶端质膜扁平化是一个内吞作用驱动的形态发生过程。对内源性标记 GFP::Rab5 动力学的定量分析显示,顶端内吞作用大量增加,与顶端形态的变化相关。这种增加伴随着管状质膜内陷的形成,这些内陷作为新生成的 Rab5 阳性内体的平台。我们确定 Rab5 效应蛋白 Rabankyrin-5 是该途径的调节剂,并证明阻断 dynamin 活性会导致管状内吞作用完全抑制、Rab5 内体消失以及表面扁平化抑制。这些数据共同证明了内吞作用在上皮发育过程中的形态发生重塑中的必要性。