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Glycobiology Advance Access published online on February 24, 2006
Glycobiology, doi:10.1093/glycob/cwj097
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received April 20, 2005
Revised January 16, 2006
Accepted February 22, 2006

Article

It Depends on the hinge: A structure-Functional Analysis of Galectin-8, a tandem-repeat type lectin

Yifat Levy 1 #, Sofia Auslender 1 #, Miriam Eisenstein 2, Roee R. Vidavski 1, Denise Ronen 1, Alexander D. Bershadsky 1, and Yehiel Zick 1 *

1 Departments of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel
2 Departments of Chemical Services, The Weizmann Institute of Science, Rehovot 76100, Israel

* To whom correspondence should be addressed.
Yehiel Zick, E-mail: yehiel.zick{at}weizmann.ac.il


  Abstract

Galectin-8, a member of the galectin family of mammalian lectins, is made of two carbohydrate-recognition-domains (CRDs), joined by a "hinge" region. Ligation of integrins by galectin-8 induces a distinct cytoskeletal organization, associated with activation of the ERK and PI3-kinase signaling cascades. Here we show that these properties of galectin-8 are mediated by the concerted action of its two CRDs and involve both protein-sugar and protein-protein interactions. Accordingly, the isolated N- or C-CRD domains of galectin-8, or galectin-8 mutated at selected residues implicated in sugar binding {E251Q; W85Y, W248Y, W(85,248)Y} exhibited reduced sugar-binding, which was accompanied by severe impairment in the capacity of these mutants to promote the adhesive, spreading and signaling functions of galectin-8. Other mutations that did not impair sugar binding {e.g. E88Q} still impeded the signaling and cell adherence functions of galectin-8. Deletion of the "hinge" region similarly impaired the biological effects of galectin-8. These results provide evidence that cooperative interactions between the two CRDs and the "hinge" domain are required for proper function of galectin-8.

Keywords: Galectins/Protein-Sugar interactions/cell adhesion/signal transduction.

# S.A. and Y.L. are equal contributors to this manuscript


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