Astrocytic but not neuronal increased expression and redistribution of parkin during unfolded protein stress.
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.
Ledesma
Maria Dolores
MD
Università degli Studi di Torino, Cavalieri Ottolenghi Scientific Institute, Torino, Italy.
Galvan
Cristian
C
Hellias
Bianca
B
Dotti
Carlos
C
Jensen
Poul Henning
PH
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
D015415:Biomarkers; D014415:Tunicamycin; D020126:Brefeldin A; D008623:Mercaptoethanol; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases