Cripto, a Multifunctional Partner in Signaling: Molecular Forms and Activities

Frédéric M. Rosa^*

Groupe Danio, U 368 INSERM, Ecole Normale Supérieure, 46, rue d'Ulm, F-75230 Paris Cedex 05, France.

Summary: Within a multicellular organism, communication between cells is essential during development to ensure proper execution of cell migration, cell fate decisions, and differentiation events. It is also essential in the adult for the coordination of many physiological functions. Cell-to-cell communications often rely on the interaction of cell surface receptors with soluble or membrane-bound ligands. Receptors or ligands may interact with additional partners to trigger specific signaling cascades inside the cell. In most cases, partners act in a specific configuration, either as a diffusible "co-ligand" or a membrane-bound co-receptor. Here, we examine the case of Cripto, a signaling molecule that has prominent functions during vertebrate development. Conflicting results have suggested that Cripto has the unusual capacity to act both as a secreted ligand and as a cell surface component to control a single signaling pathway. Here, we review the recent experiments that attempt to reconcile those results. Furthermore, three reports have described the fact that Cripto is modified by the addition of sugar residues, including a rare case of fucosylation. These modifications are essential for Cripto function, suggesting that, as is the case for other key developmental or physiological regulators such as Notch or selectins, the activity of Cripto may be controlled by the extent of its glycosylation or fucosylation (or both).

*Contact information. Telephone, 33-1-44-32-39-78; fax, 33-1-44-32-39-88; e-mail, rosa{at}wotan.ens.fr

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