This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Matzke, A.
Right arrow Articles by Orian-Rousseau, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Matzke, A.
Right arrow Articles by Orian-Rousseau, V.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2007, p. 8797-8806, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.01355-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Haploinsufficiency of c-Met in cd44–/– Mice Identifies a Collaboration of CD44 and c-Met In Vivo{triangledown}

Alexandra Matzke,1 Vardanush Sargsyan,2 Bettina Holtmann,3 Gayane Aramuni,2 Esther Asan,4 Michael Sendtner,3 Giuseppina Pace,1 Norma Howells,1 Weiqi Zhang,2 Helmut Ponta,1 and Véronique Orian-Rousseau1*

Forschungszentrum Karlsruhe, Institute for Toxicology and Genetics, Postfach 3640, 76021 Karlsruhe, Germany,1 Department of Neurophysiology and DFG-Research Center of Molecular Physiology of Brain, University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany,2 Institute for Clinical Neurobiology, University of Würzburg, Josef Schneider Strasse 11, 97080 Würzburg, Germany,3 Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstrasse 6, 97070 Würzburg, Germany4

Received 27 July 2007/ Accepted 27 September 2007

Recent evidence has shown that the activation of receptor tyrosine kinases is not only dependent on binding of their ligands but in addition requires adhesion molecules as coreceptors. We have identified CD44v6 as a coreceptor for c-Met in several tumor and primary cells. The CD44v6 ectodomain is required for c-Met activation, whereas the cytoplasmic tail recruits ERM proteins and the cytoskeleton into a signalosome complex. Here we demonstrate that c-Met (and hepatocyte growth factor and Gab1) is haploinsufficient in a cd44–/– background, as the cd44–/–; met+/– (and cd44–/–; hgf+/– and cd44–/–; gab1+/–) mice die at birth. They have impaired synaptic transmission in the respiratory rhythm-generating network and alterations in the phrenic nerve. These results are the first genetic data showing that CD44 and c-Met collaborate in vivo and that they are involved in synaptogenesis and axon myelination in the central and peripheral nervous systems.

* Corresponding author. Mailing address: Forschungszentrum Karlsruhe, Institute for Toxicology and Genetics, Postfach 3640, 76021 Karlsruhe, Germany. Phone: 497247826523. Fax: 497247823354. E-mail: veronique.orian-rousseau{at}itg.fzk.de

{triangledown} Published ahead of print on 8 October 2007.

Molecular and Cellular Biology, December 2007, p. 8797-8806, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.01355-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»