N-terminal nesprin-2 variants regulate β-catenin signalling

Zhang, Qiuping, Minaisah, Rose-Marie, Ferraro, Elisa, Li, Chen, Porter, Lauren J., Zhou, Can, Gao, Fang, Zhang, Junyi, Rajgor, Dipen, Autore, Flavia, Shanahan, Catherine M. and Warren, Derek T. (2016) N-terminal nesprin-2 variants regulate β-catenin signalling. Experimental Cell Research, 345 (2). pp. 168-179. ISSN 0014-4827

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Abstract

The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragment of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity.

Item Type:	Article
Additional Information:	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords:	cell-cell junctions,nesprin-2,scaffold protein,Β-catenin
Faculty \ School:	Faculty of Science > School of Pharmacy (former - to 2024)
UEA Research Groups:	Faculty of Science > Research Groups > Molecular and Tissue Pharmacology
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	Pure Connector
Date Deposited:	23 Nov 2016 10:00
Last Modified:	12 Dec 2024 01:40
URI:	https://ueaeprints.uea.ac.uk/id/eprint/61473
DOI:	10.1016/j.yexcr.2016.06.008

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