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

Research output: Contribution to journalArticle

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Abstract

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
Pages (from-to)35772-35786
Number of pages15
JournalJournal of Biological Chemistry
Volume282
Issue number49
DOIs
Publication statusPublished - 07-12-2007

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Glycosylphosphatidylinositols
Body Patterning
Type I Activin Receptors
Type C Phospholipases
Phosphatidylinositols
Refractory materials
Labeling
Embryonic Development
Membrane Proteins
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Watanabe, Kazuhide ; Hamada, Shin ; Bianco, Caterina ; Mancino, Mario ; Nagaoka, Tadahiro ; Gonzales, Monica ; Bailly, Veronique ; Strizzi, Luigi ; Salomon, David S. / Requirement of glycosylphosphatidylinositol anchor of Cripto-1 for trans activity as a nodal co-receptor. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 49. pp. 35772-35786.
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abstract = "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.",
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Watanabe, K, Hamada, S, Bianco, C, Mancino, M, Nagaoka, T, Gonzales, M, Bailly, V, Strizzi, L & Salomon, DS 2007, 'Requirement of glycosylphosphatidylinositol anchor of Cripto-1 for trans activity as a nodal co-receptor', Journal of Biological Chemistry, vol. 282, no. 49, pp. 35772-35786. https://doi.org/10.1074/jbc.M707351200

Requirement of glycosylphosphatidylinositol anchor of Cripto-1 for trans activity as a nodal co-receptor. / Watanabe, Kazuhide; Hamada, Shin; Bianco, Caterina; Mancino, Mario; Nagaoka, Tadahiro; Gonzales, Monica; Bailly, Veronique; Strizzi, Luigi; Salomon, David S.

In: Journal of Biological Chemistry, Vol. 282, No. 49, 07.12.2007, p. 35772-35786.

Research output: Contribution to journalArticle

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T1 - Requirement of glycosylphosphatidylinositol anchor of Cripto-1 for trans activity as a nodal co-receptor

AU - Watanabe, Kazuhide

AU - Hamada, Shin

AU - Bianco, Caterina

AU - Mancino, Mario

AU - Nagaoka, Tadahiro

AU - Gonzales, Monica

AU - Bailly, Veronique

AU - Strizzi, Luigi

AU - Salomon, David S.

PY - 2007/12/7

Y1 - 2007/12/7

N2 - 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.

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