PerspectiveMedicine

Membrane traffic en route to cancer

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Science  09 Oct 2015:
Vol. 350, Issue 6257, pp. 162-163
DOI: 10.1126/science.aad3575

Figures

  • Membrane bound.

    Growth factor receptors like PDGFRα (green) localize to the cell membrane in the absence of their ligand.

    CREDIT: WHEELER ET AL.
  • Membrane traffic control.

    Activated receptor tyrosine kinase growth factor receptors (including PDGFR) bind ligand and recruit PI3K to the plasma membrane to trigger the conversion of PI(4,5)P2 to PI(3,4,5)P3, which recruits and activates PDK1, mTORC2, and Akt (top middle); PY, phospho-tyrosine. Activated receptors are also subject to internalization by both clathrin-dependent and independent pathways (top right). The clathrin-mediated endocytosis machinery also activates Rab35, an important regulator of recycling from early endosomes. Receptors that are not recycled (top left) at early endosomes are subject to sequestration on the intraluminal vesicles of late endosomes and subsequently degraded in lysosomes (bottom right). The study by Wheeler et al. suggests an alternative role for late endosomes or lysosomes as sites of PDGFR signaling in cells that express active Rab35 mutants (bottom left).

    ILLUSTRATION: P. HUEY/SCIENCE

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