title: Ataxin-2 associates with rough endoplasmic reticulum.
abstract: Ataxin-2 is a novel protein, normally with a domain of 22 consecutive glutamine (Q) residues, which may expand beyond a threshold of (Q)(32), causing a neurodegenerative disease named Spinocerebellar ataxia type 2 (SCA2). To obtain clues about the functions of ataxin-2, we used fluorescence microscopy and centrifugation fractionation analyses. Immunocytochemical detection in non-neuronal and neuronal cells showed endogenous and transfected ataxin-2 distributed throughout the cytoplasm, with perinuclear preference and a granular appearance. Triple-labelling and confocal microscopy demonstrated co-localisation with the endoplasmic reticulum (ER) markers calreticulin, calnexin and CFP-ER. The pathogenic form of ataxin-2 with an expanded polyQ domain showed the same distribution pattern. Subcellular fractionation of mouse brain homogenates showed endogenous ataxin-2 associated with rough ER (rER) membranes, in a manner dependent on RNA, salt and phosphorylation. Our data are in agreement with recent findings that ataxin-2 directly interacts with poly(A)-binding protein (PABP), thus associating with polyribosomes under normal conditions and being recruited to stress granules under environmental stress. These data, in conjunction with the presence of Lsm domains within ataxin-2, suggest that ataxin-2 is involved in the processing of mRNA and/or the regulation of translation.
authors.affiliation: Section for Molecular Neurogenetics, Department of Neurology, University Hospital, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: van de Loo
authors.forename: Florian
authors.initials: F
authors.lastname: Eich
authors.forename: David
authors.initials: D
authors.lastname: Nonis
authors.forename: Georg
authors.initials: G
authors.lastname: Auburger
authors.forename: Joachim
authors.initials: J
authors.lastname: Nowock
mesh_terms: D000818:Animals; D000067528:Ataxins; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000378:metabolism; D004622:Embryo, Mammalian; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000648:ultrastructure*; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure; D014162:Transfection / Q000379:methods; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D000067528:Ataxins; D037282:Calreticulin; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C087574:macrogolgin; D037281:Calnexin; C097188:polyglutamine; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat