University of Oulu

Mattila, S. O., Tuusa, J. T., & Petäjä-Repo, U. E. (2016). The Parkinson’s-disease-associated receptor GPR37 undergoes metalloproteinase-mediated N-terminal cleavage and ectodomain shedding. Journal of Cell Science, 129(7), 1366–1377.

The Parkinson’s-disease-associated receptor GPR37 undergoes metalloproteinase-mediated N-terminal cleavage and ectodomain shedding

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Author: Mattila, S. Orvokki1; Tuusa, Jussi T.1; Petäjä-Repo, Ulla E.1
Organizations: 1Medical Research Center Oulu, and Cancer and Translational Medicine Research Unit, University of Oulu, Oulu FI-90014, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.7 MB)
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Language: English
Published: Company of Biologists, 2016
Publish Date: 2019-12-03


The G-protein-coupled receptor 37 ( 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 although 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 although 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 assays. These new findings on the GPR37 N-terminal limited proteolysis may help us to understand the role of this GPCR in the pathophysiology of Parkinson’s disease and in neuronal function in general.

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Series: Journal of cell science
ISSN: 0021-9533
ISSN-E: 1477-9137
ISSN-L: 0021-9533
Volume: 129
Pages: 1366 - 1377
DOI: 10.1242/jcs.176115
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Funding: This work was supported by the Medical Research Center Oulu (to U.E.P.-R.); and Magnus Ehrnrooth Foundation (to U.E.P.-R.); and by fellowship grants from Finnish Concordia Fund (to S.O.M.); Magnus Ehrnrooth Foundation (to S.O.M.); and the Finnish Parkinson Foundation (to S.O.M.).
Copyright information: © 2016. Published by The Company of Biologists Ltd. Published in this repository with the kind permission of the publisher.