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Published online before print October 16, 2003, 10.1101/gad.1127703
GENES & DEVELOPMENT 17:2624-2629, 2003
©2003 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH COMMUNICATION

Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto

Paul W. Harms and Chenbei Chang1

Department of Cell Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA

Transforming growth factor {beta} (TGF-{beta}) signals regulate multiple processes during development and in adult. We recently showed that tomoregulin-1 (TMEFF1), a transmembrane protein, selectively inhibits nodal but not activin in early Xenopus embryos. Here we report that TMEFF1 binds to the nodal coreceptor Cripto, but does not associate with either nodal or the type I ALK (activin receptor-like kinase) 4 receptor in coimmunoprecipitation assays. The inhibition of the nodal signaling by TMEFF1 in Xenopus ectodermal explants is rescued with wild-type but not mutant forms of Cripto. Furthermore, we show that the Cripto-FRL1-Cryptic (CFC) domain in Cripto, which is essential for its binding to ALK4, is also important for its interaction with TMEFF1. Our results demonstrate for the first time that nodal signaling can be regulated by a novel mechanism of blocking the Cripto coreceptor.

[Keywords: Nodal; Cripto; TGF-{beta}; tomoregulin-1]

Received July 1, 2003; revised version accepted August 26, 2003.

Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1127703.

Supplemental material is available at http://www.genesdev.org.

1 Corresponding author.
E-MAIL cchang{at}uab.edu; FAX (205) 975-5648.


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