title: Chorein, the protein responsible for chorea-acanthocytosis, interacts with β-adducin and β-actin.
abstract: Chorea-acanthocytosis (ChAc) is an autosomal, recessive hereditary disease characterized by striatal neurodegeneration and acanthocytosis, and caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene. VPS13A encodes chorein whose physiological function at the molecular level is poorly understood. In this study, we show that chorein interacts with β-adducin and β-actin. We first compare protein expression in human erythrocyte membranes using proteomic analysis. Protein levels of β-adducin isoform 1 and β-actin are markedly decreased in erythrocyte membranes from a ChAc patient. Subsequent co-immunoprecipitation (co-IP) and reverse co-IP assays using extracts from chorein-overexpressing human embryonic kidney 293 (HEK293) cells, shows that β-adducin (isoforms 1 and 2) and β-actin interact with chorein. Immunocytochemical analysis using chorein-overexpressing HEK293 cells demonstrates co-localization of chorein with β-adducin and β-actin. In addition, immunoreactivity of β-adducin isoform 1 is significantly decreased in the striatum of gene-targeted ChAc-model mice. Adducin and actin are membrane cytoskeletal proteins, involved in synaptic function. Expression of β-adducin is restricted to the brain and hematopoietic tissues, corresponding to the main pathological lesions of ChAc, and thereby implicating β-adducin and β-actin in ChAc pathogenesis.
authors.affiliation: Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Nari
authors.initials: N
authors.lastname: Shiokawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mieko
authors.initials: M
authors.lastname: Sameshima
authors.forename: Akiko
authors.initials: A
authors.lastname: Deguchi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Hayashi
authors.forename: Natsuki
authors.initials: N
authors.lastname: Sasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Sano
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D054546:Neuroacanthocytosis / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D021381:Protein Transport; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D000099291:Adducins
chemical_list: D000199:Actins; D002148:Calmodulin-Binding Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins; D000099291:Adducins; C429654:VPS13A protein, human; C497828:Vps13a protein, mouse
keywords: CBB; ChAc; Chorea-acanthocytosis; Chorein; Co-immunoprecipitation; Coomassie Brilliant Blue; FBS; HEK293; MALDI-TOF; MEME; Minimum Essential Medium Eagle; PBS containing 0.1% Tween-20; PBS-T; PMF; Tetrahymena thermophila VPS13A; TtVPS13A; VPS13A; chorea-acanthocytosis; fetal bovine serum; human embryonic kidney 293; matrix-assisted laser desorption ionization-time of flight; peptide mass fingerprint; vacuolar protein sorting 13 homolog A; β-Actin; β-Adducin