The Rab4 effector Rabip4 plays a role in the endocytotic trafficking of Glut 4 in 3T3-L1 adipocytes

Muriel Mari, Pascale Monzo, Vincent Kaddai, Frédérique Keslair, Teresa Gonzalez, Yannick Le Marchand-Brustel, Mireille Cormont

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Abstract

Insulin regulates glucose uptake in the adipocytes by modulating Glut 4 localization, a traffic pathway involving the endocytic small GTPases Rab4, Rab5, and RabThe expression of the Rab4 effector Rabip4 leads to a 30% increase in glucose uptake and Glut 4 translocation in the presence of insulin, without modifications in the basal condition. This effect was not due to modifications of Glut 4 expression or insulin signaling, suggesting that Rabip4 controls Glut 4 trafficking. We present evidence that Rabip4 defines a subdomain of early endosomes and that Rabip4 is redistributed to the plasma membrane by insulin. Rabip4 is mostly absent from structures positive for early endosome antigen 1, Rab11 or transferrin receptors and from Glut 4 sequestration compartments. However, Rabip4 vesicles can be reached by internalized transferrin and Glut 4. Thus, Rabip4 probably defines an endocytic sorting platform for Glut 4 towards its sequestration pool. The expression of a form of Rabip4 unable to bind Rab4 does not modify basal and insulin-induced glucose transport. However, it induces an increase in the amount of Glut 4 at the plasma membrane and perturbs Glut 4 traffic from endosomes towards its sequestration compartments. These observations suggest that the uncoupling between Rabip4 and Rab4 induces the insertion of Glut 4 molecules that are unable to transport glucose into the plasma membrane.
Original languageEnglish
Pages (from-to)1297-306
Number of pages10
JournalJournal of Cell Science
Volume119
Issue numberPt 7
DOIs
Publication statusPublished - 1-Apr-2006
Externally publishedYes

Keywords

  • 3T3-L1 Cells
  • Adipocytes
  • Animals
  • Cell Compartmentation
  • Cell Culture Techniques
  • Endocytosis
  • Fluorescein-5-isothiocyanate
  • Fluorescent Dyes
  • Glucose Transporter Type 4
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Confocal
  • Models, Biological
  • Mutation
  • Subcellular Fractions
  • Transferrin
  • rab4 GTP-Binding Proteins
  • GLUCOSE-TRANSPORTER GLUT4
  • TRANS-GOLGI NETWORK
  • PHOSPHATIDYLINOSITOL 3-KINASE
  • SUBCELLULAR-LOCALIZATION
  • PLASMA-MEMBRANE
  • CELL-SURFACE
  • RECYCLING COMPARTMENT
  • REGULATED TRANSPORT
  • EARLY ENDOSOMES
  • FYVE-FINGER

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