Retrograde trafficking of ?-dystroglycan from the plasma membrane to the nucleus.

ABSTRACT: ?-Dystroglycan (?-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 ?-DG to target to, and conform specific protein assemblies at the plasma membrane (PM) and nuclear envelope (NE). Although a classical NLS and importin ?/? mediated nuclear import pathway has already been described for ?-DG, the intracellular trafficking route by which ?-DG reaches the nucleus is unknown. In this study, we demonstrated that ?-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 ?-DG from the ER membrane, making it accessible for importins and nuclear import. Finally, we show that phosphorylation of ?-DG at Tyr890 is a key stimulus for ?-DG nuclear translocation. Collectively our data describe the retrograde intracellular trafficking route that ?-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.

SUBMITTER: Gracida-Jimenez V 

PROVIDER: S-EPMC5575308 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature