Journal Article

DZNE-2020-04423

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Chorein Sensitive Arrangement of Cytoskeletal Architecture.

Honisch, S. ; Gu, S. ; Müller vom Hagen, J.DZNE* ; Alkahtani, S. ; Al Kahtane, A. A. ; Tsapara, A. ; Hermann, A.DZNE* ; Storch, A.DZNE* ; Schöls, L.DZNE* ; Lang, F. ; Stournaras, C.

2015
Karger Basel

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Please use a persistent id in citations: doi:10.1159/000430363

Abstract: Chorein is a protein expressed in various cell types. Loss of function mutations of the chorein encoding gene VPS13A lead to chorea-acanthocytosis, an autosomal recessive genetic disease characterized by movement disorder and behavioral abnormalities. Recent observations revealed that chorein is a powerful regulator of actin cytoskeleton in erythrocytes, platelets, K562 and endothelial HUVEC cells.In the present study we have used Western blotting to study actin polymerization dynamics, laser scanning microscopy to evaluate in detail the role of chorein in microfilaments, microtubules and intermediate filaments cytoskeleton architecture and RT-PCR to assess gene transcription of the cytoskeletal proteins.We report here powerful depolymerization of actin microfilaments both, in erythrocytes and fibroblasts isolated from chorea-acanthocytosis patients. Along those lines, morphological analysis of fibroblasts from chorea-acanthocytosis patients showed disarranged microtubular network, when compared to fibroblasts from healthy donors. Similarly, the intermediate filament networks of desmin and cytokeratins showed significantly disordered organization with clearly diminished staining in patient's fibroblasts. In line with this, RT-PCR analysis revealed significant downregulation of desmin and cytokeratin gene transcripts.Our results provide for the first time evidence that defective chorein is accompanied by significant structural disorganization of all cytoskeletal structures in human fibroblasts from chorea-acanthocytosis patients.

Keyword(s): Actins: genetics (MeSH) ; Actins: metabolism (MeSH) ; Blood Platelets: metabolism (MeSH) ; Cytoskeletal Proteins: genetics (MeSH) ; Cytoskeletal Proteins: metabolism (MeSH) ; Cytoskeleton: metabolism (MeSH) ; Desmin: genetics (MeSH) ; Desmin: metabolism (MeSH) ; Down-Regulation: genetics (MeSH) ; Erythrocytes: metabolism (MeSH) ; Fibroblasts: metabolism (MeSH) ; Humans (MeSH) ; Neuroacanthocytosis: genetics (MeSH) ; Neuroacanthocytosis: metabolism (MeSH) ; Transcription, Genetic: genetics (MeSH) ; Vesicular Transport Proteins: metabolism (MeSH) ; Actins ; Cytoskeletal Proteins ; Desmin ; VPS13A protein, human ; Vesicular Transport Proteins

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Contributing Institute(s):

1. Clinical Neurogenetics (AG Schöls)
2. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
3. Non-Motor Symptoms in Parkinson's disease (AG Storch)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2015

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