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New roles for cripto in the assembly and localisation of nodal signalling platforms

Blanchet, Marie-Hélène
Constam, Daniel
Defense Thèse de doctorat : Univ. Genève, 2008 - Sc. 3951 - 2008/01/14
Abstract The TGFβ family member Nodal is essential during development to allocate pluripotent cells to distinct germ layers and to establish the basic body plan. To establish a signaling gradient of the transcription factors Smad2 and Smad3, Nodal forms a complex with Activin receptors that is activated with the help of the glycosylphosphosphatidyl-inositol-anchored proteoglycans Cripto or Cryptic. To elucidate the underlying mechanism, we investigated whether Cripto regulates the proteolytic maturation and/or trafficking of Nodal precursor protein. We show that Cripto captures Nodal already during secretion, partly via the propeptide, and assembles a processing complex with the proprotein convertases Furin at the cell surface. Subsequently, Cripto mediates uptake of mature Nodal via a conclathrin, noncaveolar pathway to signaling endosomes. Our results suggest that Cripto is a receptor for proprotein convertases and couples Nodal processing and signaling in target cells.
Keywords TGF-ßGPI anchor proteinProtein covertaseGastrulation
URN: urn:nbn:ch:unige-21594
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BLANCHET, Marie-Hélène. New roles for cripto in the assembly and localisation of nodal signalling platforms. Université de Genève. Thèse, 2008. https://archive-ouverte.unige.ch/unige:2159

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Deposited on : 2009-06-24

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