Cripto localizes nodal at the limiting membrane of early endosomes
| Autor: | Stéphane Baflast, Judith Klumperman, Daniel B. Constam, Viola Oorschot, Marie-Hélène Blanchet, Gabriella Minchiotti, J. Ann Le Good |
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| Předmět: |
Nodal Protein
Endosome Endosomes Biology Cripto Biochemistry Cell Line Mice Epidermal growth factor Chlorocebus aethiops Animals Humans Molecular Biology Membrane Glycoproteins Epidermal Growth Factor Effector Kinase Intracellular Membranes Cell Biology Neoplasm Proteins Protein Structure Tertiary Cell biology Membrane Cytoplasm Mutation NODAL Activin Receptors Type I hormones hormone substitutes and hormone antagonists Signal Transduction |
| Zdroj: | Science signaling 1 (2008): ra13. doi:10.1126/scisignal.1165027 info:cnr-pdr/source/autori:Blanchet M.H.; Le Good J.A.; Oorschot V.; Baflast S.; Minchiotti G.; Klumperman J.; Constam D.B./titolo:Cripto localizes Nodal at the limiting membrane of early endosomes/doi:10.1126%2Fscisignal.1165027/rivista:Science signaling/anno:2008/pagina_da:ra13/pagina_a:/intervallo_pagine:ra13/volume:1 |
| DOI: | 10.1126/scisignal.1165027 |
| Popis: | Cripto is a glycosylphosphatidylinositol (GPI)-anchored co-receptor of Nodal and several other transforming growth factor-beta (TGF-beta) family ligands. It contains an epidermal growth factor (EGF)-like motif and a Cripto-FRL1-Cryptic (CFC) domain, which are conserved in a family of EGF-CFC proteins. The EGF domain is thought to recruit Nodal, whereas the CFC domain mediates binding to activin receptor-like kinase 4 (ALK4). We found that the EGF-like motif of Cripto was not essential for its binding to Nodal. However, through residues phenylalanine 78 and glycine 71, Cripto enriched Nodal at the limiting membrane of early endosomes. Similarly, residues in the CFC domain that mediate binding of Cripto to ALK4 were required to attenuate sequestration of Nodal in the endosomal lumen. Thus, we propose that Cripto stimulates Nodal activity by localizing it at the interface of endosomes with cytoplasmic effectors. To our knowledge, Cripto is the first GPI-anchored protein shown to control intraendosomal sorting of its associated cargo. |
| Databáze: | OpenAIRE |
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