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Oligomerization Dynamics of Cell Surface Receptors in Living Cells by Total Internal Reflection Fluorescence Microscopy Combined with Number and Brightness Analysis
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Ligand dependent and independent internalization and nuclear translocation of fibroblast growth factor (FGF) receptor

John F Reilly1, Eiichi Mizukoshi, Pamela A Maher

  • 1Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA.

DNA and Cell Biology
|September 24, 2004
PubMed

Insights

Basic fibroblast growth factor (FGF-2) and its receptor (FGFR1) internalize into cells via distinct pathways, with FGFR1 nuclear translocation occurring independently of ligand binding and cell cycle-dependent.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Basic fibroblast growth factor (FGF-2) is a key signaling molecule.
  • FGF-2 interacts with high-affinity tyrosine kinase receptors (FGFR) and low-affinity heparan sulfate proteoglycans.
  • Both FGF-2 and FGFR1 translocate to the nucleus, suggesting intracellular functions.

Purpose of the Study:

  • To investigate the mechanisms of FGF-2 and FGFR1 internalization and nuclear translocation.
  • To determine the roles of clathrin-dependent and -independent endocytosis in uptake.
  • To explore the regulation of these processes, including receptor tyrosine kinase activity and cell cycle dependence.

Main Methods:

  • Utilized clathrin-dependent and -independent endocytosis assays.
  • Investigated caveolar-dependent and -independent uptake mechanisms.
  • Assessed the role of receptor tyrosine kinase activity.
  • Examined cell cycle-dependent nuclear translocation.

Main Results:

  • FGF-2 uptake involves a caveolar-dependent mechanism.
  • FGFR1 uptake is independent of caveolae and coated pits.
  • Neither FGF-2 nor FGFR1 uptake requires active receptor tyrosine kinase signaling.
  • FGFR1 nuclear translocation exhibits cell cycle dependence and can occur independently of ligand binding.

Conclusions:

  • FGF-2 and FGFR1 utilize distinct endocytic pathways for cellular uptake.
  • Receptor tyrosine kinase activity is not essential for the internalization of FGF-2 or FGFR1.
  • A novel cell cycle-dependent pathway facilitates FGFR1 nuclear translocation, independent of FGF-2 binding.

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