Fig 1: Model of RNF41 as a negative regulator of Clec9A and cross-presentation.We propose that at steady state, Clec9A interacts with RNF41, Erlin1/2 and Calreticulin. RNF41 mediates Clec9A ubiquitination at the ER and endosomes, targeting it for degradation to control Clec9A receptor levels. At early stages following dead cell uptake by DC, Clec9A is diverted away from Erlin1/2 and RNF41-mediated degradation, and is recruited with Calreticulin to dead cell-containing endosomes, to facilitate cross-presentation of dead cell Ag. At later stages following dead cell uptake, RNF41 interacts with Clec9A at endosomes to regulate Clec9A following presentation of dead cell Ag.