Riding shotgun: a dual role for the epidermal growth factor-Cripto/FRL-1/Cryptic protein Cripto in Nodal trafficking.
Nodal is a secreted protein of the transforming growth factor beta (TGFbeta) family that activates Smad2 and Smad3 transcription factors through complexes of type I and type II activin receptors and glycosyl-phosphatidylinositol-anchored coreceptors of the epidermal growth factor-like Cripto/FRL-1/Cryptic family. During early embryogenesis, it stimulates the proliferation of pluripotent progenitor cells and specifies, in a dosage-dependent manner, their subsequent allocation to distinct germ layers. Available evidence indicates that the signaling strength of Nodal is controlled at the level of endocytic uptake and turnover of activated receptor complexes in early endosomes, but insights into the underlying molecular mechanisms are still limited. In this review, I briefly survey literature on the trafficking of the related TGFbeta receptors, and I discuss recent findings indicating that endocytosis of Nodal is coupled to proteolytic processing of its precursor at the cell surface and that the maturation and internalization of Nodal need to be guided by Cripto to stabilize endosomal signaling platforms.
Constam
Daniel B
DB
Ecole Polytechnique Fédérale de Lausanne (EPFL), Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland. daniel.constam@epfl.ch
D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D055457:Nodal Protein / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
D018398:Homeodomain Proteins; D008565:Membrane Proteins; D055457:Nodal Protein; D011498:Protein Precursors; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D014157:Transcription Factors; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C110484:tdgf1 protein, zebrafish; C096788:tdgf1.3 protein, Xenopus; D004815:Epidermal Growth Factor