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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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Photoactivation approaches reveal a role for Rab11 in FGFR4 recycling and signalling

Ellen M Haugsten1, Andreas Brech, Knut Liestøl

  • 1Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, 0379, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, 0379, Norway.

Traffic (Copenhagen, Denmark)
|March 5, 2014
PubMed

Insights

Rab11 protein controls the recycling of Fibroblast Growth Factor Receptor 4 (FGFR4). This recycling is crucial for maintaining FGFR4 levels and regulating its signaling pathways, impacting cell homeostasis and cancer.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Fibroblast Growth Factor Receptor 4 (FGFR4) is vital for development and tissue homeostasis.
  • FGFR4 dysregulation (overexpression or mutations) is linked to cancer progression.
  • Receptor endocytosis regulates signaling; FGFR4 internalizes to transferrin-positive structures post-ligand binding.

Purpose of the Study:

  • To investigate the intracellular trafficking and recycling of FGFR4.
  • To determine the role of Rab11 in FGFR4 endocytosis and recycling.
  • To elucidate how Rab11-dependent FGFR4 recycling influences downstream signaling.

Main Methods:

  • Utilized a cell line with a defined pericentriolar endocytic recycling compartment.
  • Employed classical recycling assays and a photoactivatable FGFR4-PA-GFP fusion protein.
  • Performed live-cell imaging and Rab11b depletion experiments.

Main Results:

  • FGFR4 accumulates in the pericentriolar recycling compartment post-endocytosis.
  • FGFR4 recycling is dependent on Rab11; Rab11b depletion traps FGFR4 and increases its total cellular levels.
  • Rab11 depletion prolongs FGFR4 and PLC-γ phosphorylation but reduces MAPK and AKT pathway activation.

Conclusions:

  • Rab11-dependent recycling is essential for maintaining cellular FGFR4 homeostasis.
  • FGFR4 recycling regulates the nature of FGF1-induced signaling output.
  • Dysregulation of FGFR4 recycling impacts cellular signaling and may have implications for cancer therapy.
Keywords:
FGFR4Rab11endocytosisrecyclingsignalling

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