Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking

Zhou Zhou, Franziska Menzel, Tim Benninghoff, Alexandra Chadt, Chen Du, Geoffrey D. Holman, Hadi Al-Hasani

Research output: Contribution to journalLetter

9 Citations (Scopus)

Abstract

The Rab-GTPase-activating proteins (GAPs) TBC1D1 and TBC1D4 play important roles in the insulin-stimulated translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane in muscle cells and adipocytes. We identified Rab28 as a substrate for the GAP domains of both TBC1D1 and TBC1D4 in vitro. Rab28 is expressed in adipose cells and skeletal muscle, and its GTP-binding state is acutely regulated by insulin. We found that in intact isolated mouse skeletal muscle, siRNA-mediated knockdown of Rab28 decreases basal glucose uptake. Conversely, in primary rat adipose cells, overexpression of Rab28-Q72L, a constitutively active mutant, increases basal cell surface levels of an epitope-tagged HA-GLUT4. Our results indicate that Rab28 is a novel GTPase involved in the intracellular retention of GLUT4 in insulin target cells.

Original languageEnglish
Pages (from-to)88-96
Number of pages9
JournalFEBS Letters
Volume591
Issue number1
DOIs
Publication statusPublished - 1 Jan 2017

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Keywords

  • adipose tissue
  • GLUT4
  • GTPase
  • insulin signaling
  • skeletal muscle

Cite this

Zhou, Z., Menzel, F., Benninghoff, T., Chadt, A., Du, C., Holman, G. D., & Al-Hasani, H. (2017). Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking. FEBS Letters, 591(1), 88-96. https://doi.org/10.1002/1873-3468.12509