In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 7, No. 41 ( 2021-10-08)
Abstract:
Molecular pathways controlling emigration of mature thymocytes from thymus to the periphery remain incompletely understood. Here, we show that T cell–specific ablation of glycogen synthase kinase 3 (GSK3) led to severely impaired thymic egress. In the absence of GSK3, β-catenin accumulated in the cytoplasm, where it associated with and activated Akt, leading to phosphorylation and degradation of Foxo1 and downregulation of Klf2 and S1P 1 expression, thereby preventing emigration of thymocytes. A cytoplasmic membrane-localized β-catenin excluded from the nucleus promoted Akt activation, suggesting a new function of β-catenin independent of its role as a transcriptional activator. Furthermore, genetic ablation of β-catenin, retroviral expression of a dominant negative Akt mutant, and transgenic expression of a constitutively active Foxo1 restored emigration of GSK3-deficient thymocytes. Our findings establish an essential role for GSK3 in thymocyte egress and reveal a previously unidentified signaling function of β-catenin in the cytoplasm.
Type of Medium:
Online Resource
ISSN:
2375-2548
DOI:
10.1126/sciadv.abg6262
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2021
detail.hit.zdb_id:
2810933-8
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