MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation

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 localiza...

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Main Authors: Tomaz, Lucian B., Liu, Bernard A., Meroshini, M., Ong, Sheena L. M., Tan, Ee Kim, Tolwinski, Nicholas S., Williams, Christopher S., Gingras, Anne-Claude, Leushacke, Marc, Dunn, N. Ray
Other Authors: School of Biological Sciences
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Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/170810
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spelling sg-ntu-dr.10356-1708102023-10-27T08:05:58Z MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation Tomaz, Lucian B. Liu, Bernard A. Meroshini, M. Ong, Sheena L. M. Tan, Ee Kim Tolwinski, Nicholas S. Williams, Christopher S. Gingras, Anne-Claude Leushacke, Marc Dunn, N. Ray School of Biological Sciences Science::Biological sciences immunohistochemistry Mass spectrometry 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. Agency for Science, Technology and Research (A*STAR) Published version This work was funded by the Institute of Medical Biology [Agency for Science, Technology and Research (A*STAR), Singapore] as well as start-up funding provided by the Lee Kong Chian School of Medicine, Nanyang Technological University and the Ministry of Education (MOE), Singapore [Continuation Grant – Endodermal Development and Differentiation (EDD) Lab] to N.R.D. L.B.T. was initially funded by the Singapore International Graduate Award (SINGA), A*STAR Graduate Academy (A*GA). B.A.L. was funded by a Canadian Institute of Health Research postdoctoral fellowship. 2023-10-11T06:53:48Z 2023-10-11T06:53:48Z 2022 Journal Article Tomaz, L. B., Liu, B. A., Meroshini, M., Ong, S. L. M., Tan, E. K., Tolwinski, N. S., Williams, C. S., Gingras, A., Leushacke, M. & Dunn, N. R. (2022). MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation. Journal of Cell Science, 135(21). https://dx.doi.org/10.1242/jcs.259272 0021-9533 https://hdl.handle.net/10356/170810 10.1242/jcs.259272 36217793 2-s2.0-85140932673 21 135 en Journal of Cell Science © 2022 Published by The Company of Biologists Ltd. All rights reserved. This article may be downloaded for personal use only. Any other use requires prior permission of the copyright holder. The Version of Record is available online at http://doi.org/10.1242/jcs.259272 application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
immunohistochemistry
Mass spectrometry
spellingShingle Science::Biological sciences
immunohistochemistry
Mass spectrometry
Tomaz, Lucian B.
Liu, Bernard A.
Meroshini, M.
Ong, Sheena L. M.
Tan, Ee Kim
Tolwinski, Nicholas S.
Williams, Christopher S.
Gingras, Anne-Claude
Leushacke, Marc
Dunn, N. Ray
MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation
description 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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Tomaz, Lucian B.
Liu, Bernard A.
Meroshini, M.
Ong, Sheena L. M.
Tan, Ee Kim
Tolwinski, Nicholas S.
Williams, Christopher S.
Gingras, Anne-Claude
Leushacke, Marc
Dunn, N. Ray
format Article
author Tomaz, Lucian B.
Liu, Bernard A.
Meroshini, M.
Ong, Sheena L. M.
Tan, Ee Kim
Tolwinski, Nicholas S.
Williams, Christopher S.
Gingras, Anne-Claude
Leushacke, Marc
Dunn, N. Ray
author_sort Tomaz, Lucian B.
title MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation
title_short MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation
title_full MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation
title_fullStr MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation
title_full_unstemmed MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation
title_sort mcc is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation
publishDate 2023
url https://hdl.handle.net/10356/170810
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