Modulation of developmental signals by endocytosis: different means and many ends.
Recent advances have highlighted the importance of endocytic processes in regulating the activity and distribution of developmental signals. Classically, signalling is downregulated by endocytosis and subsequent trafficking to lysosomes (e.g. Notch, Hedgehog, Roundabout). However, endocytosis can also have a positive role in signalling. For example, endocytosis of Delta, the ligand of Notch, is needed for activation of the signal. In the case of signalling by Hedgehog, endocytic trafficking segregates an inhibitory receptor (Patched) from the positive effector (Smoothened). Endosomes could also be the site where signalling is activated (e.g. transforming growth factor beta). Finally, endocytosis could power the transport of morphogens along epithelia.
Piddini
Eugenia
E
National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
Vincent
Jean-Paul
JP
D000818:Animals; D019521:Body Patterning / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D053823:Hedgehog Proteins; D006801:Humans; D021381:Protein Transport / Q000502:physiology; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
D053823:Hedgehog Proteins; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors