title: Chorein Sensitive Arrangement of Cytoskeletal Architecture.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Physiology, University of Tx00FC;bingen, Tx00FC;bingen, Germany.
authors: Sabina
authors: S
authors: Honisch
authors: Shuchen
authors: S
authors: Gu
authors: Jennifer Müller
authors: JM
authors: Vom Hagen
authors: Saad
authors: S
authors: Alkahtani
authors: Abdullah A
authors: AA
authors: Al Kahtane
authors: Anna
authors: A
authors: Tsapara
authors: Andreas
authors: A
authors: Hermann
authors: Alexander
authors: A
authors: Storch
authors: Ludger
authors: L
authors: Schöls
authors: Florian
authors: F
authors: Lang
authors: Christos
authors: C
authors: Stournaras
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D003893:Desmin / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004912:Erythrocytes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D054546:Neuroacanthocytosis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D003893:Desmin; C429654:VPS13A protein, human; D033921:Vesicular Transport Proteins