Galectin-3, a novel centrosome-associated protein, required for epithelial morphogenesis.
Galectin-3 is a beta-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.
Koch
Annett
A
Department of Cell Biology and Cell Pathology, Philipps University, D-35033 Marburg, Germany.
Poirier
Francoise
F
Jacob
Ralf
R
Delacour
Delphine
D
D000818:Animals; D002502:Centrioles / Q000648:ultrastructure; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004848:Epithelium / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D037502:Galectin 3 / Q000378:metabolism*; D020868:Gene Silencing; D051379:Mice; D009024:Morphogenesis; D034741:RNA, Small Interfering / Q000378:metabolism
D037502:Galectin 3; D034741:RNA, Small Interfering