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Sci Rep. 2017 Aug 29;7(1):9906. doi: 10.1038/s41598-017-09972-x.

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

Author information

1
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Ciudad de México, Mexico, Mexico.
2
Laboratory of Protein Dynamics and Signaling, Center for Cancer Research-Frederick, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
3
Instituto de Fisiología Celular, Universidad Nacional Autónoma de Mexico, Ciudad de Mexico, Mexico, Mexico.
4
Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, United Kingdom.
5
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Ciudad de México, Mexico, Mexico. bcisnero@cinvestav.mx.

Abstract

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 Tyr890 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.

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