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Human sorCS1 binds sortilin and hampers its cellular functions
- Source :
- Larsen, J V, Hermey, G, Sørensen, E S, Prabakaran, T, Christensen, E I, Gliemann, J, Madsen, P & Petersen, C M 2014, ' Human sorCS1 binds sortilin and hampers its cellular functions ', Biochemical Journal, vol. 457, no. 2, pp. 277–288 . https://doi.org/10.1042/BJ20130386
- Publication Year :
- 2013
- Publisher :
- Portland Press Ltd., 2013.
-
Abstract
- Sortilin and sorCS1 [sortilin-related Vps10p (vacuolar protein sorting/targeting protein 10) domain-containing receptor 1], both members of the Vps10p-D (Vps10p-domain) receptor family, are synthesized as precursor proteins and are converted into their mature form by enzymatic cleavage of a short N-terminal propeptide. SorCS1 does not bind its propeptide, but sortilin is able to bind not just its own propeptide, but also that of sorCS1. In the present study we show that the propeptide region of sorCS1 contains two separate sites for binding to sortilin and that only one of these sites is removed from human (as opposed to mouse) sorCS1 during processing. This leaves mature human sorCS1 with a sortilin-binding N-terminus, which allows formation of a complex between the two receptors in solution and on cell membranes. Furthermore, we find that the interaction with sorCS1 has a pronounced effect on sortilin's ability to mediate the cellular uptake of alternative ligands, and to hamper its facilitation of CNTF (ciliary neutrophic factor) signalling and the induction of phosphorylated STAT3 (signal transducer and activator of transcription 3). Thus the present study reveals a novel regulatory mechanism and suggest an entirely new role for sorCS1 as a modulator of sortilin function.
- Subjects :
- Cell
Receptors, Cell Surface
CHO Cells
Biology
Ciliary neurotrophic factor
Cleavage (embryo)
Biochemistry
Cricetulus
Cricetinae
medicine
Animals
Humans
Protein Precursors
Receptor
Protein precursor
Molecular Biology
Vacuolar protein sorting
chemistry.chemical_classification
Cell Membrane
Cell Biology
Cell biology
Adaptor Proteins, Vesicular Transport
HEK293 Cells
Enzyme
medicine.anatomical_structure
chemistry
biology.protein
STAT protein
Protein Processing, Post-Translational
Protein Binding
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 457
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....2759d91b0bde3aff3e742fb9ff9bb491