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Gracida-Jimenez, Viridiana; Mondragon-Gonzalez, Ricardo; Velez-Aguilera, Griselda; Vasquez-Limeta, Alejandra; Laredo-Cisneros, Marco S; de Dios Gomez-Lopez, Juan; Vaca, Luis; Gourlay, Sarah C; Jacobs, Laura A; Winder, Steve J; Cisneros, Bulmaro (2017)

RETROGRADE TRAFFICKING OF BETA-DYSTROGLYCAN FROM THE PLASMA MEMBRANE TO THE NUCLEUS

Sci Rep 7():
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β-Dystroglycan (β-DG) is a transmembrane protein with critical roles in cell adhesion, cytoskeleton remodeling and nuclear architecture. This functional diversity is attributed to the ability of β-DG to target to, and conform specific protein assemblies at the plasma membrane (PM) and nuclear envelope (NE). Although a classical NLS and importin α/β mediated nuclear import pathway has already been described for β-DG, the intracellular trafficking route by which β-DG reaches the nucleus is unknown. In this study, we demonstrated that β-DG undergoes retrograde intracellular trafficking from the PM to the nucleus via the endosome-ER network. Furthermore, we provided evidence indicating that the translocon complex Sec61 mediates the release of β-DG from the ER membrane, making it accessible for importins and nuclear import. Finally, we show that phosphorylation of β-DG at Tyr(890) is a key stimulus for β-DG nuclear translocation. Collectively our data describe the retrograde intracellular trafficking route that β-DG follows from PM to the nucleus. This dual role for a cell adhesion receptor permits the cell to functionally connect the PM with the nucleus and represents to our knowledge the first example of a cell adhesion receptor exhibiting retrograde nuclear trafficking and having dual roles in PM and NE.