Chorein, the protein responsible for chorea-acanthocytosis, interacts with ?-adducin and ?-actin.

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 ?-adducin and ?-actin. We first compare protein expression in human erythrocyte membranes using proteomic analysis. Protein levels of ?-adducin isoform 1 and ?-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 ?-adducin (isoforms 1 and 2) and ?-actin interact with chorein. Immunocytochemical analysis using chorein-overexpressing HEK293 cells demonstrates co-localization of chorein with ?-adducin and ?-actin. In addition, immunoreactivity of ?-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 ?-adducin is restricted to the brain and hematopoietic tissues, corresponding to the main pathological lesions of ChAc, and thereby implicating ?-adducin and ?-actin in ChAc pathogenesis.
Mesh Terms:
Actins, Animals, Brain, Calmodulin-Binding Proteins, Disease Models, Animal, Erythrocyte Membrane, HEK293 Cells, Humans, Immunoprecipitation, Mice, Mice, Inbred C57BL, Nerve Tissue Proteins, Neuroacanthocytosis, Protein Binding, Protein Transport, Vesicular Transport Proteins
Biochem. Biophys. Res. Commun.
Date: Nov. 08, 2013
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