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

6 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

Fingerprint

GTPase-Activating Proteins
Muscle
Insulin
Substrates
Cells
rab GTP-Binding Proteins
Skeletal Muscle
Facilitative Glucose Transport Proteins
GTP Phosphohydrolases
Cell membranes
Guanosine Triphosphate
Small Interfering RNA
Rats
Epitopes
Adipocytes
Muscle Cells
Glucose
Cell Membrane

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

Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking. / Zhou, Zhou; Menzel, Franziska; Benninghoff, Tim; Chadt, Alexandra; Du, Chen; Holman, Geoffrey D.; Al-Hasani, Hadi.

In: FEBS Letters, Vol. 591, No. 1, 01.01.2017, p. 88-96.

Research output: Contribution to journalLetter

Zhou, Z, Menzel, F, Benninghoff, T, Chadt, A, Du, C, Holman, GD & Al-Hasani, H 2017, 'Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking', FEBS Letters, vol. 591, no. 1, pp. 88-96. https://doi.org/10.1002/1873-3468.12509
Zhou, Zhou ; Menzel, Franziska ; Benninghoff, Tim ; Chadt, Alexandra ; Du, Chen ; Holman, Geoffrey D. ; Al-Hasani, Hadi. / Rab28 is a TBC1D1/TBC1D4 substrate involved in GLUT4 trafficking. In: FEBS Letters. 2017 ; Vol. 591, No. 1. pp. 88-96.
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