Function of the Mon1-Ccz1 complex on endosomes.

Rabs exist in two forms: the inactive GDP- and the active GTP-bound form. GEF proteins mediate the exchange of GDP for GTP and thereby activate Rabs. Although GEFs share a common action, which involves the opening of the Rab nucleotide binding site, they do not contain a conserved catalytic domain. Longin domains have been either found in several GEFs (TRAPP, DENN) or predicted by sequence analyses (Mon1-Ccz1, BLOC-3). At least in TRAPP, they serve as a platform for interaction with a GTPase. We recently generated a model of the predicted longin domains of the Mon1-Ccz1 complex based upon the structure of the respective TRAPP subunits. This allowed us to identify activity-related important regions of the complex. Moreover, we analyzed the GEF activity of Mon1-Ccz1 in the presence of membranes and uncovered that certain acidic phospholipids support the recruitment of the GEF complex. In this commentary, we will discuss our findings in a broader context.