Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes.
The three GTPases Rab5, Rab4 and Rab11 regulate sequential transport steps along the endocytic/recycling pathway, and occupy distinct membrane domains on early and recycling endosomes. To address the mechanisms that regulate communication between such domains, we searched for proteins that interact with both Rab5 and Rab4. Here, we report that Rabenosyn-5, a previously identified Rab5 effector, also binds to Rab4. Rabenosyn-5 overexpression increased the association between Rab5 and Rab4 endosomal domains and decreased the fraction of Rab4- and Rab11-positive structures. This redistribution was accompanied by a faster rate of transferrin recycling from early endosomes to the cell surface and reduced transport to Rab11-containing perinuclear recycling endosomes. These effects depend on the ability of Rabenosyn-5 to interact with Rab4. We propose that divalent Rab effectors regulate protein sorting and recycling by connecting Rab domains on early endosomes.
de Renzis
Stefano
S
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse, 01307 Dresden, Germany.
Sönnichsen
Birte
B
Zerial
Marino
M
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002417:Cattle; D002458:Cell Fractionation; D002460:Cell Line; D006224:Cricetinae; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D018613:Microscopy, Confocal; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
D002352:Carrier Proteins; D004815:Epidermal Growth Factor; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014168:Transferrin; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C416362:RBSN protein, human