Dynamics of Rab7b-dependent transport of sorting receptors.
The small GTPase Rab7b localizes to late endosomes-lysosomes and to the Golgi, regulating the transport between these two intracellular compartments. We have recently demonstrated that depletion of Rab7b causes missorting of the cation-independent mannose 6-phosphate receptor (CI-MPR), suggesting that Rab7b may control the trafficking of this receptor. Here we further investigated the function of this small GTPase with special attention to its role in the trafficking of sorting receptors and dynamics in living cells. Using endosome-to-Golgi retrieval assays we show that Rab7b is involved not only in CI-MPR transport but also in the MPRs independent pathway. Indeed, we find that it regulates and interacts with sortilin, a mannose 6-phosphate-independent sorting receptor. CI-MPR and sortilin are sorted from the trans-Golgi network (TGN) in tubular structures and the expression of Rab7b mutants or its silencing reduces CI-MPR and sortilin tubulation. In addition, the constitutively active mutant Rab7b Q67L impairs the formation of carriers from TGN. Collectively, our observations show for the first time that Rab7b is required for transport from endosomes to the TGN, not only of the CI-MPR, but also of sortilin, and that alterations in this transport result in impaired carrier formation from TGN.
Centre for Immune Regulation, Department of Molecular Biosciences, University of Oslo, Blindernveien 31, 0371, Oslo, Norway.
Cinzia
C
Progida
Morten S
MS
Nielsen
Gerbrand
G
Koster
Cecilia
C
Bucci
Oddmund
O
Bakke
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D020125:Mutation, Missense; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D021381:Protein Transport; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2 / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000090802:rab7 GTP-Binding Proteins; D021601:trans-Golgi Network / Q000378:metabolism; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; D000099183:Sortilin