Galectin-3, a novel centrosome-associated protein, required for epithelial morphogenesis

Autor: Delphine Delacour, Annett Koch, Ralf Jacob, Françoise Poirier
Přispěvatelé: Department of cell biology and cell pathology, University of Marburg, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Molecular Biology of the Cell
Molecular Biology of the Cell, American Society for Cell Biology, 2010, 21 (2), pp.219-31. ⟨10.1091/mbc.E09-03-0193⟩
ISSN: 1939-4586
1059-1524
DOI: 10.1091/mbc.E09-03-0193⟩
Popis: We investigated the role of galectin-3 on polarization of epithelial renal cells, using three-dimensional cultures of MDCK cells and also galectin-3 null mutant mouse kidneys. Collectively, data show that the absence of galectin-3 influences the stabilization of centrosomes and primary cilia, with effects on epithelial cell organization.
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.
Databáze: OpenAIRE