title: Astrocytic but not neuronal increased expression and redistribution of parkin during unfolded protein stress.
abstract: Parkin is a ubiquitin ligase that facilitates proteasomal protein degradation and is involved in a common autosomal recessive form of Parkinson's disease. Its expression is part of the unfolded protein response in cell lines where its overexpression protects against unfolded protein stress. How parkin expression is regulated in brain primary cells under stress situations is however, less well established. Here, the cellular and subcellular localization of parkin under basal conditions and during unfolded protein stress was investigated in primary cultures of rat astrocytes and hippocampal neurons. Immunofluorescense microscopy and biochemical analysis demonstrated that parkin is mainly associated with the endoplasmic reticulum (ER) in hippocampal neurons while it is associated with Golgi membranes, the nuclei and light vesicles in astrocytes. The constitutive parkin expression was high in neurons as compared with astrocytes. However, unfolded protein stress elicited a selective increase in astrocytic parkin expression and a change in distribution, whereas neuronal parkin remained largely unmodified. The cell specific differences argue in favour of different cellular binding sites and substrates for the protein and a pathogenic role for astrocytes in Parkinson's disease caused by parkin dysfunction.
authors.affiliation: Università degli Studi di Torino, Cavalieri Ottolenghi Scientific Institute, Torino, Italy.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Ledesma
authors.forename: Cristian
authors.initials: C
authors.lastname: Galvan
authors.forename: Bianca
authors.initials: B
authors.lastname: Hellias
authors.forename: Carlos
authors.initials: C
authors.lastname: Dotti
authors.forename: Poul Henning
authors.initials: PH
authors.lastname: Jensen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D020126:Brefeldin A / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008025:Ligases / Q000032:analysis / Q000378:metabolism*; D008623:Mercaptoethanol / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D017510:Protein Folding; D051381:Rats; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases
chemical_list: D015415:Biomarkers; D014415:Tunicamycin; D020126:Brefeldin A; D008623:Mercaptoethanol; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases