Modulation of Receptor Recycling and Degradation by the Endosomal Kinesin KIF16B

Cell. 2005 May 6;121(3):437-50. doi: 10.1016/j.cell.2005.02.017.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Transport
  • Cloning, Molecular
  • Endosomes / metabolism*
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism
  • HeLa Cells
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism*
  • Liposomes / metabolism
  • Microtubules / metabolism
  • Molecular Motor Proteins / metabolism
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phylogeny
  • Protein Binding
  • Protein Transport
  • Receptors, Cell Surface / metabolism*
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Transferrin / metabolism
  • rab5 GTP-Binding Proteins / metabolism

Substances

  • KIF16B protein, human
  • Liposomes
  • Molecular Motor Proteins
  • Receptors, Cell Surface
  • Recombinant Proteins
  • Transferrin
  • Epidermal Growth Factor
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Kinesin
  • rab5 GTP-Binding Proteins