Affiliation:
1. Medical Research Center Oulu and Department of Anatomy and Cell Biology, University of Oulu, FI-90014 Oulu, Finland
Abstract
The G protein-coupled receptor GPR37 has been implicated in the juvenile form of Parkinson's disease, in dopamine signalling and in the survival of dopaminergic cells in animal models. The structure and function of the receptor, however, have remained enigmatic. Here, we demonstrate that while GPR37 matures and is exported from the endoplasmic reticulum in a normal manner upon heterologous expression in HEK293 and SH-SY5Y cells, its long extracellular N-terminus is subject to metalloproteinase-mediated limited proteolysis between E167 and Q168. The proteolytic processing is a rapid and efficient process that occurs constitutively. Moreover, the GPR37 ectodomain is released from cells by shedding, a phenomenon rarely described for GPCRs. Immunofluorescence microscopy further established that while full-length receptors are present in the secretory pathway until the trans-Golgi network, GPR37 is expressed at the cell surface predominantly in the N-terminally truncated form. This notion was verified by flow cytometry and cell surface biotinylation. These novel findings on the GPR37 N-terminal limited proteolysis may help to understand the role of this GPCR in the pathophysiology of Parkinson's disease and in neuronal function in general.
Funder
Medical Research Center Oulu
Magnus Ehrnrooth Foundation
Finnish Concordia Fund
Finnish Parkinson Foundation
Publisher
The Company of Biologists
Cited by
27 articles.
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