Regulatory Mechanism Discovered for Fibril Formation in Nerve Cells in Hereditary Movement Disorder
Within the protein Atx-3, the scientists succeeded in
identifying one motif consisting of four basic amino acids which serves as a
recognition site for VCP-interaction. VCP plays a role in vital processes in
the cell, e.g. in the degradation of dysfunctional or no longer needed
proteins. As demonstrated in vitro
and also in experiments involving the Drosophila
fruit fly, excess concentrations of VCP in proportion to Atx-3 suppress the
formation of fibrils. By contrast, if VCP concentrations are too low in
proportion to Atx-3, the fibril formation is stimulated. Thus, high VCP
concentrations reduce Atx-3 protein aggregation in the retinal cells of the
fruit fly and, in this way, prevent the degeneration of these cells. The
molecular mechanism regulating how VCP mitigates the toxicity of pathogenic
Atx-3 is still unclear. Here, further research promises to yield additional
insights.
*An arginine/lysine-rich motif is
crucial for VCP/p97-mediated modulation of ataxin-3 fibrillogenesis
Annett Boeddrich1,8,
Sébastien Gaumer2,8,9, Annette Haacke3, Nikolay Tzvetkov3,
Mario Albrecht4, Bernd O Evert5, Eva C Müller1,
Rudi Lurz6, Peter Breuer3, Nancy Schugardt1,
Stephanie Plaßmann1, Kexiang Xu2, John M Warrick2,
Jaana Suopanki1, Ullrich Wüllner5, Ronald Frank7,10,
Ulrich F Hartl3,10, Nancy M Bonini2,10 and Erich E Wanker1,10,*
1Department of Neuroproteomics,
Max Delbrueck Center for Molecular Medicine (MDC), Berlin, Germany, 2Department
of Biology, Howard Hughes Medical Institute, University of Pennsylvania,
Philadelphia, PA,USA, 3Max Planck Institute for Biochemistry,
Martinsried, Germany, 4Max Planck Institute for Informatics,
Saarbrücken, Germany, 5Department of Neurology, University of Bonn,
Bonn, Germany, 6Max Planck Institute for Molecular Genetics, Berlin,
Germany and 7Department of Chemical Biology, GBF, Braunschweig,
Germany
10
These are senior authors
Barbara Bachtler
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