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Get off my back! Rapid receptor internalization through circular dorsal ruffles

James D Orth1, Mark A McNiven

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Cancer Research
|December 6, 2006
PubMed

Insights

New research reveals that circular dorsal ruffles, not clathrin-coated pits, mediate receptor tyrosine kinase (RTK) internalization. This actin-dependent pathway impacts cell growth and may be altered in tumor cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Receptor tyrosine kinases (RTKs) regulate critical cellular processes like growth and motility.
  • RTK internalization and trafficking are traditionally linked to clathrin-coated pits.
  • Nonclathrin-mediated endocytosis pathways for RTKs are less understood.

Purpose of the Study:

  • To investigate novel pathways for RTK internalization beyond clathrin-coated pits.
  • To elucidate the role of dynamic membrane structures in RTK trafficking.
  • To explore the implications of these pathways in cancer cell biology.

Main Methods:

  • Observation of dynamic, transient endocytic membrane structures (circular dorsal ruffles/dorsal waves).
  • Assessment of protein dependence (dynamin, cortactin) and independence (clathrin, caveolin).
  • Analysis of actin cytoskeleton involvement in dorsal wave formation.

Main Results:

  • Circular dorsal ruffles selectively internalize a significant portion of RTKs from cell surfaces.
  • This process relies on dynamin and cortactin, and actin cytoskeleton remodeling.
  • Clathrin and caveolin are not required for dorsal wave-mediated RTK internalization.
  • Dorsal wave formation may be less frequent in tumor cells.

Conclusions:

  • Circular dorsal ruffles represent a significant nonclathrin pathway for RTK internalization.
  • Actin cytoskeleton dynamics are crucial for this endocytic process.
  • Altered dorsal wave formation in tumor cells could impact RTK signaling and cell growth, presenting potential therapeutic targets.

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