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Activation of the Ca2+sensing receptor and the PKC/WNK4 downstream signaling cascade induces incorporation of ZO-2 to tight junctions and its separation from 14-3-3
- Source :
- Molecular Biology of the Cell. 30:2377-2398
- Publication Year :
- 2019
- Publisher :
- American Society for Cell Biology (ASCB), 2019.
-
Abstract
- Zonula occludens-2 (ZO-2) is a tight junction (TJ) cytoplasmic protein, whose localization varies according to cell density and Ca2+in the media. In cells cultured in low calcium (LC), ZO-2 displays a diffuse cytoplasmic distribution, but activation of the Ca2+sensing receptor (CaSR) with Gd3+triggers the appearance of ZO-2 at the cell borders. CaSR downstream signaling involves activation of protein kinase C, which phosphorylates and activates with no lysine kinase-4 that phosphorylates ZO-2 inducing its concentration at TJs. In LC, ZO-2 is protected from degradation by association to 14-3-3 proteins. When monolayers are transferred to normal calcium, the complexes ZO-2/14-3-3ζ and ZO-2/14-3-3σ move to the cell borders and dissociate. The 14-3-3 proteins are then degraded in proteosomes, whereas ZO-2 integrates to TJs. From the plasma membrane residual ZO-2 is endocyted and degradaded in lysosomes. The unique region 2 of ZO-2, and S261 located within a nuclear localization signal, are critical for the interaction with 14-3-3 ζ and σ and for the efficient nuclear importation of ZO-2. These results explain the molecular mechanism through which extracellular Ca2+triggers the appearance of ZO-2 at TJs in epithelial cells and reveal the novel interaction between ZO-2 and 14-3-3 proteins, which is critical for ZO-2 protection and intracellular traffic.
- Subjects :
- 0303 health sciences
Tight junction
Cell growth
Cell Biology
Biology
Cell biology
03 medical and health sciences
0302 clinical medicine
Cytoplasm
Extracellular
Signal transduction
Molecular Biology
030217 neurology & neurosurgery
Intracellular
Protein kinase C
Nuclear localization sequence
030304 developmental biology
Subjects
Details
- ISSN :
- 19394586 and 10591524
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi...........8584edbd295f706867bb642db434c87b
- Full Text :
- https://doi.org/10.1091/mbc.e18-09-0591