Xenopus Lefty requires proprotein cleavage but not N-linked glycosylation to inhibit nodal signaling.

Westmoreland JJ, Takahashi S, Wright CV
Dev Dyn. 2007 236 (8): 2050-61

PMID: 17584861 · DOI:10.1002/dvdy.21210

The Nodal and Nodal-related morphogens are utilized for the specification of distinct cellular identity throughout development by activating discrete target genes in a concentration-dependant manner. Lefty is a principal extracellular antagonist involved in the spatiotemporal regulation of the Nodal morphogen gradient during mesendoderm induction. The Xenopus Lefty proprotein contains a single N-linked glycosylation motif in the mature domain and two potential cleavage sites that would be expected to produce long (Xlefty(L)) and short (Xlefty(S)) isoforms. Here we demonstrate that both isoforms were secreted from Xenopus oocytes, but that Xlefty(L) is the only isoform detected when embryonic tissue was analyzed. In mesoderm induction assays, Xlefty(L) is the functional blocker of Xnr signaling. When secreted from oocytes, vertebrate Lefty molecules were N-linked glycosylated. However, glycan addition was not required to inhibit Xnr signaling and did not influence its movement through the extracellular space. These findings demonstrate that Lefty molecules undergo post-translational modifications and that some of these modifications are required for the Nodal inhibitory function.

(c) 2007 Wiley-Liss, Inc.

MeSH Terms (15)

Animals Binding Sites Dihydropyridines Embryo, Nonmammalian Embryonic Induction Glycosylation Left-Right Determination Factors Mesoderm Oocytes Protein Isoforms Protein Processing, Post-Translational Signal Transduction Transforming Growth Factor beta Xenopus Xenopus Proteins

Connections (2)

This publication is referenced by other Labnodes entities: