Bicc1 Polymerization Regulates the Localization and Silencing of Bound mRNA.
Bottom Line: In addition, defective polymerization decreases Bicc1 stability and thus indirectly attenuates inhibition of Dishevelled 2 in the Wnt/β-catenin pathway.Importantly, aberrant C-terminal extension of the SAM domain in bpk mutant Bicc1 phenocopied these defects.We conclude that polymerization is a novel disease-relevant mechanism both to stabilize Bicc1 and to present associated mRNAs in specific silencing platforms.
Affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), SV ISREC, Lausanne, Switzerland.Show MeSH
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Mentions: Bicc1-deficient mice are born with cysts in their kidneys and pancreas and dilated liver bile ducts (25, 27, 54). Concordant with a function in renal morphogenesis, the Bicc1 protein is expressed in the newborn mouse kidney cortex (25, 27). However, the distribution of Bicc1 in this or other tissues has not been resolved at a subcellular level. To address this, we stained frozen sections of postnatal kidneys and livers using a novel custom anti-Bicc1 antibody that specifically reacts with the tissues of wild-type but not Bicc1−/− mice (see Fig. S2 in the supplemental material). Lotus tetragonolobus lectin (LTL), which is expressed in proximal tubules, was used to mark cortical renal structures, whereas the cholangiocytes of liver bile ducts were marked by cytokeratin-19 (CK19). High-resolution imaging revealed a nonhomogeneous distribution of endogenous Bicc1 in clusters of cytoplasmic puncta both in renal proximal tubule cells and in cholangiocytes (Fig. 1). The volumes of these puncta varied from 0.05 to 0.6 μm3, similar to those of cytoplasmic foci detected by anti-HA staining of tagged Bicc1 in transfected HEK293T cells, although the latter were larger, on average, possibly due to overexpression rather than alternative fixation or the use of anti-HA antibody instead of anti-SAM antibody (see Fig. S3 in the supplemental material). These data show that Bicc1 clusters in cytoplasmic puncta and that this pattern is not restricted to one tissue but could be a general feature of Bicc1.
Affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), SV ISREC, Lausanne, Switzerland.