MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation.
| Autor: | Tomaz LB; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore.; School of Biological Sciences, Nanyang Technological University, 637551, Singapore.; Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 138648, Singapore., Liu BA; Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada., Meroshini M; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore., Ong SLM; Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 138648, Singapore., Tan EK; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore.; Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 138648, Singapore., Tolwinski NS; Division of Science, Yale-NUS College, 138527, Singapore., Williams CS; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA., Gingras AC; Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada., Leushacke M; Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 308232, Singapore., Dunn NR; Lee Kong Chian School of Medicine, Nanyang Technological University, 308232, Singapore.; School of Biological Sciences, Nanyang Technological University, 637551, Singapore.; Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), 138648, Singapore.; Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 308232, Singapore. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of cell science [J Cell Sci] 2022 Nov 01; Vol. 135 (21). Date of Electronic Publication: 2022 Oct 28. |
| DOI: | 10.1242/jcs.259272 |
| Abstrakt: | The gene mutated in colorectal cancer (MCC) encodes a coiled-coil protein implicated, as its name suggests, in the pathogenesis of hereditary human colon cancer. To date, however, the contributions of MCC to intestinal homeostasis and disease remain unclear. Here, we examine the subcellular localization of MCC, both at the mRNA and protein levels, in the adult intestinal epithelium. Our findings reveal that Mcc transcripts are restricted to proliferating crypt cells, including Lgr5+ stem cells, where the Mcc protein is distinctly associated with the centrosome. Upon intestinal cellular differentiation, Mcc is redeployed to the apical domain of polarized villus cells where non-centrosomal microtubule organizing centers (ncMTOCs) are positioned. Using intestinal organoids, we show that the shuttling of the Mcc protein depends on phosphorylation by casein kinases 1δ and ε, which are critical modulators of WNT signaling. Together, our findings support a role for MCC in establishing and maintaining the cellular architecture of the intestinal epithelium as a component of both the centrosome and ncMTOC. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.) |
| Databáze: | MEDLINE |
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