Quercetin accumulates in nuclear structures and triggers specific gene expression in epithelial cells.

Quercetin is a flavonol modifying a number of cell processes in different cell lines. Here, we present evidence that nonconjugated quercetin enters cells possibly via organic anion transporter polypeptides and quickly accumulates in the nucleus where it concentrates at distinct foci. Furthermore, it induces major transcriptional events with a high number of transcripts being modified over time and about 2200 transcripts being continuously influenced by the agent. The latter transcripts are related to cell cycle and adhesion, xenobiotic metabolism, immune-related factors and transcription. In addition, quercetin up-regulates the expression of estrogen receptors α and ß. The overall outcome on cell fate is reflected by an inhibition of cell proliferation, cell cycle arrest in the G1 phase and reduction of the cells' migratory potential due to actin cytoskeleton disorganization. Finally, we report that the flavonol modifies the transcription and/or activity of numerous transcription factors. In conclusion, our data support the idea that quercetin may actively accumulate in discrete cell structures and exert more than just antioxidant actions on epithelial cells by regulating mechanisms related to gene transcription.

Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers.

Myelination results in a highly segregated distribution of axonal membrane proteins at nodes of Ranvier. Here, we show the role in this process of TAG-1, a glycosyl-phosphatidyl-inositol-anchored cell adhesion molecule. In the absence of TAG-1, axonal Caspr2 did not accumulate at juxtaparanodes, and the normal enrichment of shaker-type K+ channels in these regions was severely disrupted, in the central and peripheral nervous systems. In contrast, the localization of protein 4.1B, an axoplasmic partner of Caspr2, was only moderately altered. TAG-1, which is expressed in both neurons and glia, was able to associate in cis with Caspr2 and in trans with itself. Thus, a tripartite intercellular protein complex, comprised of these two proteins, appears critical for axo-glial contacts at juxtaparanodes. This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo-glial interactions.