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Vol. 21, Issue 2, 219-231, January 15, 2010
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*Department of Cell Biology and Cell Pathology, Philipps University, D-35033 Marburg, Germany;
Jacques Monod Institute, UMR-CNRS7592, Paris Diderot University, 75013 Paris, France
Submitted March 9, 2009;
Revised October 30, 2009;
Accepted November 5, 2009
Monitoring Editor: Benjamin Margolis
Galectin-3 is a β-galactoside–binding protein widely expressed in all epithelia where it is involved in tissue homeostasis and cancer progression. We recently reported unique abnormalities in the identity of membrane domains in galectin-3 null mutant mice, suggesting that galectin-3 may participate in epithelial polarity program. We investigated the potential role of galectin-3 on early events in polarization of epithelial renal cells, using three-dimensional cultures of MDCK cells and also galectin-3 null mutant mouse kidneys. We show that depletion in galectin-3 systematically leads to severe perturbations of microtubular network associated with defects in membrane compartimentation, both in vitro and in vivo. Moreover, the absence of galectin-3 impinges on the morphology of the primary cilium, which is three times longer and unusually shaped. By immunological and biochemical approaches, we could demonstrate that endogenous galectin-3 is normally associated with basal bodies and centrosomes, where it closely interacts with core proteins, such as centrin-2. However, this association transiently occurs during the process of epithelial polarization. Interestingly, galectin-3–depleted cells contain numerous centrosome-like structures, demonstrating an unexpected function of this protein in the formation and/or stability of the centrosomes. Collectively, these data establish galectin-3 as a key determinant in epithelial morphogenesis via its effect on centrosome biology.
Present addresses:
Charité-Universitätsmedizin Berlin, CCM, Institut für Biochemie, Monbijoustraße 2, 10117 Berlin, Germany;
Institut Jacques-Monod, CNRS UMR 7592, Université Paris 7, Bâtiment Buffon, 15 Rue Hélène Brion, 75013 Paris.
Address correspondence to: Ralf Jacob (jacob{at}staff.uni-marburg.de) or Delphine Delacour (delacour.delphine{at}ijm.univ-paris-diderot.fr)