Dynamin inhibitors impair endocytosis and mitogenic signaling of PDGF

Łukasz Sadowski1, Kamil Jastrzębski, Yannis Kalaidzidis

  • 1Laboratory of Cell Biology, International Institute of Molecular and Cell Biology, Warsaw, Poland.

Insights

Researchers developed a new tool to track Platelet-Derived Growth Factor (PDGF) endocytosis. Dynamin-independent pathways contribute to PDGF uptake, and dynamin is crucial for PDGF-induced cell proliferation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Platelet-Derived Growth Factor (PDGF) regulates critical cellular processes like proliferation and differentiation.
  • Endocytosis plays a key role in modulating growth factor signaling, but PDGF endocytosis is poorly understood.
  • A lack of tools to visualize internalized PDGF has hindered research.

Purpose of the Study:

  • To develop a tool for tracking internalized PDGF using microscopy.
  • To quantitatively analyze the endocytosis and endosomal trafficking of PDGF-BB in human fibroblasts.
  • To investigate the role of dynamin in PDGF uptake and downstream signaling.

Main Methods:

  • Development of a novel microscopy-based tool for tracking internalized PDGF-BB.
  • Quantitative analysis of PDGF-BB internalization and trafficking in human fibroblasts.
  • Assessment of PDGF signaling and cellular responses under dynamin inhibition.

Main Results:

  • PDGF-BB internalization and endosomal trafficking were quantitatively analyzed using the developed tool.
  • PDGF can be internalized via both dynamin-dependent and dynamin-independent pathways.
  • Inhibition of dynamin selectively impaired PDGF-induced STAT3 signaling, MYC expression, and cell cycle entry, despite moderate effects on overall endocytosis.

Conclusions:

  • Endocytic trafficking components can selectively regulate specific growth factor signaling pathways.
  • Dynamin activity is essential for PDGF-induced mitogenesis, impacting downstream signaling and cell proliferation.
  • The developed tool facilitates the study of PDGF endocytosis and trafficking.

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