PX-FERM proteins: A link between endosomal trafficking and signaling?

Endosomes are the primary organelle where decisions are made as to whether endocytosed proteins will be sorted into degradative trafficking pathways or recycled back to the plasma membrane. This balance between cellular uptake and recycling regulates the plasma membrane composition and is therefore critical for many cellular processes such as nutrient uptake, neuronal transmission and cell migration.1 In addition to its well-known role in membrane trafficking, the endosome is increasingly being recognized as a critical cellular domain for regulated cell signaling. We recently showed that several proteins that regulate endosomal recycling, SNX17, SNX27 and SNX31 are structurally and functionally related.2 These proteins use an unusual FERM domain to bind specific endosomal cargo molecules, and most interestingly, we also found that these proteins use the same FERM domain to associate with the activated Ras small GTPase. Here we speculate on the potential dual role of the PX-FERM proteins in endosomal transport and as scaffolds that may be involved in endosomal Ras signaling processes.