Enhancement of Notch Receptor Maturation and Signaling Sensitivity by Cripto-1

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Enhancement of Notch Receptor Maturation and Signaling Sensitivity by Cripto-1

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Title: Enhancement of Notch Receptor Maturation and Signaling Sensitivity by Cripto-1
Author: Watanabe, Kazuhide; Nagaoka, Tadahiro; Bianco, Caterina; Gonzales, Monica; Castro, Nadia P.; Rangel, Maria Cristina; Sakamoto, Kei; Callahan, Robert; Salomon, David S.; Lee, Joseph M.; Sun, Youping

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Citation: Watanabe, Kazuhide, Tadahiro Nagaoka, Joseph M. Lee, Caterina Bianco, Monica Gonzales, Nadia P. Castro, Maria Cristina Rangel, et al. 2009. Enhancement of Notch receptor maturation and signaling sensitivity by Cripto-1. The Journal of Cell Biology 187(3): 343-353.
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Abstract: Nodal and Notch signaling pathways play essential roles in vertebrate development. Through a yeast two-hybrid screening, we identified Notch3 as a candidate binding partner of the Nodal
coreceptor Cripto-1. Coimmunoprecipitation analysis confirmed the binding of Cripto-1 with all four mammalian Notch receptors. Deletion analyses revealed that the binding of Cripto-1 and Notch1 is mediated by the Cripto-1/FRL-1/Cryptic domain of Cripto-1 and the C-terminal region of epidermal growth factor–like repeats of Notch1. Binding of Cripto-1 to Notch1 occurred mainly in the endoplasmic reticulum–Golgi network. Cripto-1 expression resulted in the recruitment of Notch1 protein into lipid raft microdomains and enhancement of the furin-like protein convertase-mediated proteolytic maturation of Notch1(S1 cleavage). Enhanced S1 cleavage resulted in the sensitization to ligand-induced activation of Notch signaling.
In addition, knockdown of Cripto-1 expression in human and mouse embryonal carcinoma cells desensitized the ligand-induced Notch signaling activation. These results suggest a novel role of Cripto-1 in facilitating the posttranslational maturation of Notch receptors.
Published Version: doi:10.1083/jcb.200905105
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779239/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4621598
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