The findings, which include uncovering one of the key molecules involved, provide a new way of thinking about how cells take on the shape required to perform different tasks – and not only in fruit flies.
“This outward-facing – or apical – surface is the main difference between different kinds of epithelial cell,” says De Renzis. “The cells on your skin are smooth, but the ones lining your intestine have lots of ‘fingers’ like our fly embryos, and we know for instance that some bowel diseases involve problems in those ‘fingers’.”
For this work, Piotr Fabrowski in De Renzis’ lab developed a new strategy for imaging the fruit fly embryo and Aleksandar Necakov, a joint post-doctoral fellow in the De Renzis and John Briggs labs at EMBL, combined light and electron microscopy to see how different the swallowed membrane tubes are from the vesicles usually formed in endocytosis.
Fabrowski, P., Necakov, A.S., Mumbauer, S., Loeser, E., Reversi, A., Streichan, S., Briggs, J.A.G. & De Renzis, S. Tubular endocytosis drives remodelling of the apical surface during epithelial morphogenesis in Drosophila. Published online in Nature Communications on 7 August 2013. 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.