Systems biology of the secretory pathway: What have we learned so far?

Several RNAi screens were performed in search for regulators of the secretory pathway. These screens were performed in different organisms and cell lines and relied on different readouts. Therefore, they have only little overlap among their hits, leading to the question of what we have learned from this approach so far and how these screens contributed towards an integrative understanding of the endomembrane system. The aim of this review is to revisit these screens and discuss their strengths and weaknesses as well as potential reasons for their failure to overlap with each other. As with secretory trafficking, RNAi screens were also performed on other cellular processes such as cell migration and autophagy, both of which were shown to be intimately linked to secretion. Another aim of this review is to compare the outcome of the RNAi screens on secretion, autophagy and cell migration and ask whether the functional genomic approaches have uncovered potential mechanistic insights into the links between these processes.