FERARI is required for Rab11-dependent endocytic recycling

• Published in: Nature cell biology Vol. 22; no. 2; pp. 213 - 224
• Main Authors: Solinger, Jachen A., Rashid, Harun-Or, Prescianotto-Baschong, Cristina, Spang, Anne
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2020; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 13/109; 13/31; 13/44; 13/51; 13/89; 14; 14/19; 14/28; 14/34; 14/35; 14/63; 38/77; 45; 45/29; 45/41; 631/80; 631/80/313; 631/80/642; 631/80/642/1776; 631/80/85/2361; 64; 64/11; 82; 82/111; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Animals, Genetically Modified; Biodegradation; Biomedical and Life Sciences; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cancer Research; Cell Biology; Cell Communication; Cell interactions; Developmental Biology; Endocytosis - genetics; Endosomes; Endosomes - metabolism; Gene Expression Regulation; Guanosine triphosphatases; HEK293 Cells; HeLa Cells; Humans; Intestines - cytology; Life Sciences; Membrane fusion; Membrane proteins; Membranes; Modules; Molecular Imaging; Oocytes - cytology; Oocytes - metabolism; Protein Transport; Protein turnover; Proteins; Proteolysis; Recycling (Waste, etc.); SNAP receptors; Sorting Nexins - genetics; Sorting Nexins - metabolism; Stem Cells; Tethering; Vesicular Transport Proteins - genetics; Vesicular Transport Proteins - metabolism
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/s41556-019-0456-5

Endosomal transport is essential for cellular organization and compartmentalization and cell–cell communication. Sorting endosomes provide a crossroads for various trafficking pathways and determine recycling, secretion or degradation of proteins. The organization of these processes requires membrane-tethering factors to coordinate Rab GTPase function with membrane fusion. Here, we report a conserved tethering platform that acts in the Rab11 recycling pathways at sorting endosomes, which we name factors for endosome recycling and Rab interactions (FERARI). The Rab-binding module of FERARI consists of Rab11FIP5 and rabenosyn-5/RABS-5, while the SNARE-interacting module comprises VPS45 and VIPAS39. Unexpectedly, the membrane fission protein EHD1 is also a FERARI component. Thus, FERARI appears to combine fusion activity through the SM protein VPS45 with pinching activity through EHD1 on SNX-1-positive endosomal membranes. We propose that coordination of fusion and pinching through a kiss-and-run mechanism drives cargo at endosomes into recycling pathways. Solinger et al. show that FERARI is a conserved tethering platform that mediates Rab11-dependent recycling at sorting endosomes.