In cooperation with the Center for Information Services and High Performance Computing (ZIH) at the Dresden University of Technology, scientists from the Max Planck Institute of Molecular Cell Biology and Genetics therefore applied a new strategy to identify and characterize genes involved in endocytosis. For that a combination of high-resolution microscopy and quantitative image analysis enabled the scientists to investigate the effects of a large number of genes. From their findings the scientists also hope to derive significant information about how infections could be prevented and diseases treated in future.

Cells take up material from the outside by pinching off from their cell membrane vesicles that transport substances to different cellular organelles. Depending on what they contain, these vesicles and organelles -- also known as endosomes -- are transported to different locations within the cell, where their content is either re-distributed or broken down to recycle the basic building blocks. Endosomes are organised in a complex transport network that ensures a correct transport of a wide variety of substances towards their proper intracellular destination. However, the exact details of how, for instance, signalling molecules arrive at their respective destinations and transmit their information from the cell membrane to the nucleus are still largely unknown.

The new investigation strategy provided the scientists with previously unimagined insights into the highly complicated processes that take place in the cell. They discovered in their images, for example, that a failure of certain genes cause the arrest of vesicles in the cell periphery rather than being transported to the centre of the cell. Furthermore, different substances such as nutrients and growth factors are apparently guided to their destination by different set of genes and endocytosis is controlled by various signalling pathways. At the same time, the cells use endocytosis to carefully adjust the quantity of signal molecules on the cell membrane and in the endosomes -- endocytosis and signalling pathways thus influence each other. All in all, more than 4,000 genes are directly or indirectly involved in endocytosis. "Our findings demonstrate that cells don't simply go out and ingest just any substances, handling them in the same manner. On the contrary, they have a very precise definition of what they need when and in what quantity, and also where it needs to get to in the cell," says Marino Zerial, Director at the Max Planck Institute of Molecular Cell Biology and Genetics.

Impaired endocytosis can cause disease

The enormous number of genes involved also reflects the significance of endocytosis for the cell and the entire organism. For example, signalling of important metabolic regulators like insulin depend on endocytosis. Immune cells, for their part, swallow pathogens and digest them inside endosomes. Therefore, it might one day be possible to prevent dangerous infections if the endocytosis of viruses and bacteria could be selectively inhibited or if the pathogens could be destroyed more effectively in the endosomes. Consequently, if the role of the different genes in endocytosis were known, it would in future be easier to develop potential treatments for these diseases.