Modulation of receptor recycling and degradation by the endosomal kinesin KIF16B.
Different classes of endosomes exhibit a characteristic intracellular steady-state distribution governed by interactions with the cytoskeleton. We found a kinesin-3, KIF16B, that transports early endosomes to the plus end of microtubules in a process regulated by the small GTPase Rab5 and its effector, the phosphatidylinositol-3-OH kinase hVPS34. In vivo, KIF16B overexpression relocated early endosomes to the cell periphery and inhibited transport to the degradative pathway. Conversely, expression of dominant-negative mutants or ablation of KIF16B by RNAi caused the clustering of early endosomes to the perinuclear region, delayed receptor recycling to the plasma membrane, and accelerated degradation. These results suggest that KIF16B, by regulating the plus end motility of early endosomes, modulates the intracellular localization of early endosomes and the balance between receptor recycling and degradation. We propose that this mechanism could have important implications for signaling.
Hoepfner
Sebastian
S
Max-Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.
Severin
Fedor
F
Cabezas
Alicia
A
Habermann
Bianca
B
Runge
Anja
A
Gillooly
David
D
Stenmark
Harald
H
Zerial
Marino
M
D000595:Amino Acid Sequence; D001692:Biological Transport; D003001:Cloning, Molecular; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D021381:Protein Transport; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014168:Transferrin / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016547:Kinesins; D008081:Liposomes; D020409:Molecular Motor Proteins; D019869:Phosphatidylinositol 3-Kinases; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D014168:Transferrin; D020696:rab5 GTP-Binding Proteins; C504670:KIF16B protein, human