Abstract
The dynactin p150glued subunit, encoded by the gene DCTN1 is part of the dynein–dynactin motor protein complex responsible for retrograde axonal transport. This subunit is a candidate modifier for neurodegenerative diseases, in particular motoneuron and extrapyramidal diseases. Based on an extensive screening effort of all 32 exons in more than 2,500 ALS/MND patients, patients suffering from Parkinsonian Syndromes and controls, we investigated 24 sequence variants of p150 in cell-based studies. We used both non-neuronal cell lines and primary rodent spinal motoneurons and report on cell biological abnormalities in five of these sequence alterations and also briefly report on the clinical features. Our results suggest the presence of biological changes caused by some p150 mutants pointing to a potential pathogenetic significance as modifier of the phenotype of the human disease.
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Acknowledgments
The authors would like to thank Sabine Seltenheim and Ursula Pika-Hartlaub for excellent technical support. Cooperating neurologic departments: Prof. Dr. Kwieczinksi, University of Warsaw, Poland and Prof. Dr. P. Andersen, University of Umeå, Sweden. This work was supported by the Packard Foundation and the Deutsche Forschungsgemeinschaft (KFO 142), SFB497/B8 to TMB and DFG BO1718/4-1 to StL and TMB, the Helmholtz Gesellschaft (VH-VI-510 to S.L. and TMB), BMBF (MND-Net to S.L and TMB), the German Foundation for Heart Research (F/34/11 to StL), the Else-Kröner-Fresenius-Stiftung (2011_A200 to S.L.), EURO-MOTOR (to ACL and StL.), and Boehringer-Ingelheim BIU (N5 to StL.). Sponsors had no influence on study design or the collection, analysis and interpretation of data.
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M. Stockmann, M. Meyer-Ohlendorf, A. C. Ludolph and S. Liebau contributed equally to this work
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Stockmann, M., Meyer-Ohlendorf, M., Achberger, K. et al. The dynactin p150 subunit: cell biology studies of sequence changes found in ALS/MND and Parkinsonian Syndromes. J Neural Transm 120, 785–798 (2013). https://doi.org/10.1007/s00702-012-0910-z
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DOI: https://doi.org/10.1007/s00702-012-0910-z