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Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes

Tuomas A Tolvanen1, Surjya Narayan Dash1, Zydrune Polianskyte-Prause1

  • 1Department of Pathology, University of Helsinki, 00290 Helsinki, Finland.

Journal of Cell Science
|November 8, 2015
PubMed

Insights

The adapter protein CD2-associated protein (CD2AP) is crucial for insulin-regulated glucose transporter 4 (Glut4) trafficking and glucose uptake. Its absence impairs Glut4 vesicle transport and reduces cellular glucose uptake.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Physiology

Background:

  • The adapter protein CD2-associated protein (CD2AP) plays roles in cellular signaling and vesicle trafficking.
  • Insulin-dependent glucose transporter 4 (Glut4) is essential for glucose uptake, particularly in response to insulin.
  • Understanding the regulation of Glut4 trafficking is key to metabolic research.

Purpose of the Study:

  • To investigate the role of CD2AP in the trafficking of Glut4 and subsequent glucose uptake.
  • To elucidate the molecular mechanisms by which CD2AP influences Glut4 localization and function.

Main Methods:

  • Utilized CD2AP knockout (CD2AP(-/-)) podocytes and wild-type controls.
  • Performed live-cell imaging of HA-Glut4-GFP.
  • Conducted subcellular membrane fractionations.
  • Investigated protein complex formation using co-fractionation and co-immunoprecipitation assays.

Main Results:

  • CD2AP(-/-) podocytes exhibited reduced basal glucose uptake and failed to increase uptake upon insulin stimulation.
  • Live-cell imaging showed perinuclear clustering of HA-Glut4-GFP in CD2AP(-/-) cells.
  • CD2AP co-fractionated with Glut4, IRAP, and sortilin within Glut4 storage vesicles (GSVs).
  • CD2AP interacts with GGA2 and clathrin, facilitating Glut4 sorting to GSVs and proper clathrin recycling.

Conclusions:

  • CD2AP is essential for the proper trafficking and insulin-stimulated exocytosis of Glut4 storage vesicles.
  • CD2AP mediates Glut4 trafficking by interacting with GGA2 and clathrin, and by connecting clathrin to the actin cytoskeleton.
  • Defects in CD2AP function lead to impaired glucose uptake due to disrupted GSV trafficking and clathrin recycling.
Keywords:
ActinClathrinGGA2Glut4 trafficking

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