Requirement of glycosylphosphatidylinositol anchor of Cripto-1 for trans activity as a nodal co-receptor

Kazuhide Watanabe, Shin Hamada, Caterina Bianco, Mario Mancino, Tadahiro Nagaoka, Monica Gonzales, Veronique Bailly, Luigi Strizzi, David S. Salomon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Cripto-1 (CR-1) has an indispensable role as a Nodal co-receptor for patterning of body axis in embryonic development. CR-1 is reported to have a paracrine activity as a Nodal co-receptor, although CR-1 is primarily produced as a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Regulation of cis and trans function of CR-1 should be important to establish the precise body patterning. However, the mechanism by which GPI-anchored CR-1 can act in trans is not well known. Here we confirmed the paracrine activity of CR-1 by fluorescent cell-labeling and immunofluorescent staining. We generated COOH-terminal-truncated soluble forms of CR-1 based on the attachment site for the GPI moiety (ω-site), which we identified in the present study. GPI-anchored CR-1 has a significantly higher activity than COOH-terminal- truncated soluble forms to induce Nodal signal in trans as well as in cis. Moreover, transmembrane forms of CR-1 partially retained their ability to induce Nodal signaling only when type I receptor Activin-like kinase 4 was overexpressed. NTERA2/D1 cells, which express endogenous CR-1, lost the cell-surface expression of CR-1 after phosphatidylinositol-phospholipase C treatment and became refractory to stimulation of Nodal. These observations suggest that GPI attachment of CR-1 is required for the paracrine activity as a Nodal co-receptor.

Original languageEnglish (US)
Pages (from-to)35772-35786
Number of pages15
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Dec 7 2007

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology


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