FERARI: a novel tether involved in endocytic recycling

Endosomal transport is essential for cellular organization and compartmentalization and cell-cell communication. Sorting endosomes provide a crossroad for various trafficking pathways and determine recycling, secretion or degradation of proteins. The organisation of these processes requires membrane tethering factors to coordinate Rab GTPase function with membrane fusion. Here, we report a conserved tethering complex that acts in the Rab11 recycling pathways at sorting endosomes, which we name FERARI (Factor for Endosome Recycling And Retromer Interactions). The Rab binding module of FERARI consists of Rab11FIP5/RFIP-2 and rabenosyn-5/RABS-5, while the SNARE interacting module comprises VPS45 and VIPAS39/SPE-39. Unexpectedly, the membrane fission protein EHD1/RME-1 is also a FERARI component. Thus, FERARI appears to combine fusion activity through the SM protein VPS45 with pinching activity through EHD1/RME-1 on SNX-1-positive endosomal membranes. We propose that coordination of fusion and pinching through a kiss-and-stay mechanism drives sorting at endosomes into recycling pathways.