Elsevier

Experimental Cell Research

Volume 274, Issue 1, 10 March 2002, Pages 138-148
Experimental Cell Research

Regular Article
Nuclear Localization of the Tight Junction Protein ZO-2 in Epithelial Cells

https://doi.org/10.1006/excr.2001.5457Get rights and content

Abstract

The tight junction constitutes the major barrier to solute and water flow through the paracellular space of epithelia and endothelia. It is formed by transmembrane proteins and submembranous molecules such as the MAGUKs ZOs. We have previously found that several MAGUKs, including those of the tight (ZO-1, ZO-2, and ZO-3) and septate junction (tamou and Dlg), contain one or two nuclear sorting signals located at their first PDZ and GK domains. Now we show that these proteins also contain a nuclear export signal and focus our study on the nuclear membrane shuttling of ZO-2. In sparse cultures this molecule concentrates at the nucleus in clusters, where it partially colocalizes with splicing factor SC35. Nuclear staining diminishes as the monolayer acquires confluence through a process sensitive to the nuclear export inhibitor leptomycin B. Nuclear localization can be induced by impairing cell–cell contacts, by mechanical injury. ZO-2 that shuttles from the cell periphery into the nucleus is not newly synthesized but originates from a preexistent pool. The movement of this protein is mediated by the actin cytoskeleton.

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      Citation Excerpt :

      ZO-2 is a 160 kD MAGUK protein with a dual localization. Thus in quiescent epithelial cells ZO-2 is present at the TJ, whereas in proliferating cells it localizes both at the TJ and the nucleus [28]. At the nucleus, ZO-2 accumulates in speckles, co-localizes with the essential splicing factor SC-35, and inhibits gene transcription by association to molecular complexes formed by transcription factors and histone deacetylases [29,30].

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