The London Tube is the city’s lifeline, transporting people to every corner and back. Similarly, the body relies on networks of tubes – tubular organs such as the gut, windpipe and glands – to transport such bodily substances as solutes, hormones, nutrients, oxygen and waste products.
The inner lining of the tubular organ is composed of a layer of specialized epithelial, or “outer,” cells, which, among other things, control the secretion of useful substances into the organ’s “tunnel.” To enter the tunnel, these substances must first make their way to the exposed edge of the epithelial cells. Special proteins within the cells lead the substances in the right direction, but how they do this is not exactly clear.
An epithelial cell’s tunnel-facing edge is always rich in “cables” made from a common protein called filamentous actin. “Who” makes these actin cables? How do they become localized only in the cell’s tunnel-facing edge? What is their function there? New research recently published in Developmental Cell by Prof. Ben-Zion Shilo, together with (then) research student Dr. R’ada Massarwa and Dr. Eyal Schejter of the Weizmann Institute’s Molecular Genetics Department, has provided, for the first time, possible answers to these questions
Working with fruit fly embryos, the team discovered that a protein called Dia was responsible for the specialized actin structures. When the scientists removed the gene for Dia production, they found signs of filament production along other parts of the cell, but no cable structures were being formed along its tunnel-facing edge. Further experiments revealed that in order for Dia to carry out its function, it first has to be activated by other types of proteins. These Dia-activating proteins are bound to the tunnel-facing side of the epithelial cell, thus ensuring the cables’ polarized distribution.
How exactly are the actin cables used? The scientists noted that in cells where cables weren’t produced, no substances were secreted into the organ’s tunnel. In other words, the actin cables seem to be the “route” the substances need to travel to arrive at the tunnel. The team discovered that the substances are “shuttled” on a type of “cable car” – a motor protein called myosin V – which transports them along the actin cable and drops them off at the tunnel entrance, from which they eventually get secreted.
“Our research shows that this mechanism for secretion in the fruit fly embryo is employed in different tubular organs, regardless of their size and function,” said Shilo. “For our next study, we plan to check whether the same mechanism is found in mammalian species, including humans. We hope that these insights will help us gain a better understanding of the mechanisms involved in secretion by tubular organs and, on a practical level, to improve doctors’ ability to deal with pathological situations that are caused by a failure of the secretion process.”
Prof. Ben-Zion Shilo’s research is supported by the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Mary Ralph Designated Philanthropic Fund; the Carolito Stiftung; La Fondation Raphael et Regina Levy; and the estate of Georg Galai. Prof. Shilo is the incumbent of the Hilda and Cecil Lewis Professorial Chair of Molecular Genetics.