Calnuc Function in Endosomal Sorting of Lysosomal Receptors.
| Autor: | Larkin H; Department of Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada., Costantino S; Centre de recherche de l'Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, H1T 2M, Canada., Seaman MN; Cambridge Institute for Medical Research, Department of Clinical Biochemistry, Wellcome Trust/MRC Building, Addenbrookes Hospital, University of Cambridge, Cambridge, CB2 0XY, UK., Lavoie C; Department of Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. |
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| Jazyk: | angličtina |
| Zdroj: | Traffic (Copenhagen, Denmark) [Traffic] 2016 Apr; Vol. 17 (4), pp. 416-32. Date of Electronic Publication: 2016 Feb 12. |
| DOI: | 10.1111/tra.12374 |
| Abstrakt: | Calnuc is a ubiquitous Ca(2+)-binding protein present on the trans-Golgi network (TGN) and endosomes. However, the precise role of Calnuc in these organelles is poorly characterized. We previously highlighted the role of Calnuc in the transport of LRP9, a new member of a low-density lipoprotein (LDL) receptor subfamily that cycles between the TGN and endosomes. The objective of this study was to explore the role of Calnuc in the endocytic sorting of mannose-6-phosphate receptor (MPR) and Sortilin, two well-characterized lysosomal receptors that transit between the TGN and endosomes. Using biochemical and microscopy assays, we showed that Calnuc depletion [by small interfering RNA (siRNA)] causes the misdelivery to and degradation in lysosomes of cationic-independent mannose-6-phosphate receptor (CI-MPR) and Sortilin due to a defect in the endosomal recruitment of retromers, which are key components of the endosome-to-Golgi retrieval machinery. Indeed, we demonstrated that Calnuc depletion impairs the activation and membrane association of Rab7, a small G protein required for the endosomal recruitment of retromers. Overall, our data indicate a novel role for Calnuc in the endosome-to-TGN retrograde transport of lysosomal receptors through the regulation of Rab7 activity and the recruitment of retromers to endosomes. (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
| Databáze: | MEDLINE |
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