New publiction by team leader Arne Möller and colleagues

The title of the paper is: Hidden Twins: SorCS Neuroreceptors Form Stable Dimers

2017.09.05 | Kathrine Hennings

SorCS1, SorCS2 and SorCS3 belong to the Vps10p-domain family of multiligand receptors. Genetic and functional studies have linked SorCS receptors to psychiatric disorders, Alzheimer's disease and type 2 diabetes, demonstrating critical roles in neuronal functionality and metabolic control. Surprisingly, their structural composition has so far not been studied. Here we have characterized SorCS1, SorCS2 and SorCS3 using biochemical methods and electron microscopy. We found that their purified extracellular domains co-exist in stable dimeric and monomeric populations. This was supported by co-immunoprecipitation experiments, where membrane-bound dimers were successfully pulled down from cell lysate. While dimers were virtually unbreakable, dimerization of the monomeric population was promoted through enzymatic deglycosylation. We conclude that post-translational modifications, specifically the degree and pattern of glycosylation, regulate the oligomeric state of the protein. Hence, cells may dictate ligand specificity by controlling the ratio between monomers and dimers and, therefore, regulate the multiple functions of SorCS receptors.

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Dovile Januliene (1, 2), Arulmani Manavalan (3), Peter Lund Ovesen (4), Karen-Marie Pedersen (4), Søren Thirup (5), Anders Nykjær (3, 4), Arne Moeller (1, 2)

1 Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438 Frankfurt am Main, Germaný

2 DANDRITE, iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark

3 Mayo Clinic, 4500 San Pablo Rd S, Jacksonville, FL 32224, USA

4 DANDRITE, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, 8000 Aarhus C, Denmark

5 MIND Centre, Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus C, Denmark

 

 

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