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Cytosolic GPR37, but not GPR37L1, multimerization and its reversal by Parkin: A live cell imaging study
Author(s) -
Li Tianyi,
Oasa Sho,
Ciruela Francisco,
Terenius Lars,
Vukojević Vladana,
Svenningsson Per
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202101213r
Subject(s) - parkin , cytoplasm , förster resonance energy transfer , endosome , chemistry , cytosol , microbiology and biotechnology , live cell imaging , hek 293 cells , endocytosis , biophysics , receptor , cell , fluorescence , biology , biochemistry , parkinson's disease , medicine , disease , physics , pathology , quantum mechanics , enzyme
Biochemical data have shown aggregated G protein‐coupled receptor 37 (GPR37) in the cytoplasm and Lewy bodies in Parkinson's disease (PD). Properly folded GPR37 at the plasma membrane appears to be neuroprotective. GPR37, and its homologue GPR37L1, are orphan G protein‐coupled receptors and their homo‐ and hetero‐dimers have not been established. We therefore examined GPR37 and GPR37L1 dimerization and extended studies of multimerization of GPR37 to live cells. In this study, we investigated GPR37 and GPR37L1 dimerization and multimerization in live cells using three quantitative imaging methods: Fluorescence Cross‐Correlation Spectroscopy, Förster Resonance Energy Transfer, and Fluorescence Lifetime Imaging Microscopy. Our data show that GPR37 and GPR37L1 form homo‐ and heterodimers in live N2a cells. Importantly, aggregation of GPR37, but not GPR37L1, was identified in the cytoplasm, which could be counteracted by Parkin overexpression. These data provide further evidence that GPR37 participate in cytosolic aggregation processes implicated in PD pathology.