Research ArticleCell Biology

Cripto Localizes Nodal at the Limiting Membrane of Early Endosomes

Sci. Signal.  11 Nov 2008:
Vol. 1, Issue 45, pp. ra13
DOI: 10.1126/scisignal.1165027

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The Right Sort of Signal

Signaling by the transforming growth factor–β (TGF-β) family member Nodal is important in tissue patterning during embryonic development, among other processes. Nodal activates the transcription factors Smad 2 and 3 by binding to its receptor activin receptor–like kinase 4 (ALK4) and its co-receptor Cripto, a glycosylphosphatidylinositol (GPI)–anchored protein. Cripto is known to be important in the proteolytic processing and endocytosis of Nodal in lipid rafts. Here, Blanchet et al. show that Cripto thereafter is also needed in early endosomes to activate ALK4 by attenuating the sorting of Nodal to intraendosomal vesicles.