MCC is a centrosomal protein that relocalizes to non-centrosomal apical sites during intestinal cell differentiation.
J Cell Sci
; 135(21)2022 11 01.
Article
em En
| MEDLINE
| ID: mdl-36217793
ABSTRACT
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Centrossomo
/
Centro Organizador dos Microtúbulos
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article