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First published online 16 April 2008
doi: 10.1242/dev.019323

Development 135, 1813-1822 (2008)
Published by The Company of Biologists 2008
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Regulation of TGF-β signalling by N-acetylgalactosaminyltransferase-like 1

Patrick Herr*,{dagger}, Ganna Korniychuk{dagger}, Yukiyo Yamamoto{ddagger}, Kristina Grubisic and Michael Oelgeschläger§

Max-Planck Institute of Immunobiology, Stübeweg 51, D-79108 Freiburg, Germany.

§ Author for correspondence (e-mail: oelgeschlaeg{at}immunbio.mpg.de)

Accepted 19 March 2008

The TGF-β superfamily of secreted signalling molecules plays a pivotal role in the regulation of early embryogenesis, organogenesis and adult tissue homeostasis. Here we report the identification of Xenopus N-acetylgalactosaminyltransferase-like 1 (xGalntl-1) as a novel important regulator of TGF-β signalling. N-acetylgalactosaminyltransferases mediate the first step of mucin-type glycosylation, adding N-acetylgalactose to serine or threonine side chains. xGalntl-1 is expressed in the anterior mesoderm and neural crest territory at neurula stage, and in the anterior neural crest, notochord and the mediolateral spinal cord at tailbud stage. Inhibition of endogenous xGalntl-1 protein synthesis, using specific morpholino oligomers, interfered with the formation of anterior neural crest, anterior notochord and the spinal cord. Xenopus and mammalian Galntl-1 inhibited Activin as well as BMP signalling in the early Xenopus embryo and in human HEK 293T cells. Gain- and loss-of-function experiments showed that xGalntl-1 interferes with the activity of the common TGF-β type II receptor ActR-IIB in vivo. In addition, our biochemical data demonstrated that xGalntl-1 specifically interferes with the binding of ActR-IIB to Activin- and BMP-specific type I receptors. This inhibitory activity of xGalntl-1 was dependent on mucin-type glycosylation, as it was sensitive to the chemical inhibitor benzyl-GalNAc. These studies reveal an important role of a N-acetylgalactosaminyltransferase in the regulation of TGF-β signalling. This novel regulatory mechanism is evolutionarily conserved and, thus, might provide a new paradigm for the regulation of TGF-β signalling in vertebrates.

Key words: TGF-β, Mucin, O-linked glycosylation, BMP, Nodal




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P. Herr, G. Korniychuk, Y. Yamamoto, K. Grubisic, and M. Oelgeschlager
Regulation of TGF-{beta} signalling by N-acetylgalactosaminyltransferase-like 1
J. Cell Sci., May 15, 2008; 121(10): e1006 - e1006.
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