The dynactin p150 subunit: cell biology studies of sequence changes found in ALS/MND and Parkinsonian Syndromes

• Published in: Journal of Neural Transmission Vol. 120; no. 5; pp. 785 - 798
• Main Authors: Stockmann, Marianne, Meyer-Ohlendorf, Marie, Achberger, Kevin, Putz, Stefan, Demestre, Maria, Yin, Haishan, Hendrich, Corinna, Linta, Leonhard, Heinrich, Jutta, Brunner, Cornelia, Proepper, Christian, Kuh, Georges F., Baumann, Bernd, Langer, Torben, Schwalenstöcker, Birgit, Braunstein, Kerstin E., von Arnim, Christine, Schneuwly, Stephan, Meyer, Thomas, Wong, Philip C., Boeckers, Tobias M., Ludolph, Albert C., Liebau, Stefan
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01-05-2013; Springer Nature B.V
• Subjects: Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - pathology; Animals; Apoptosis - drug effects; Apoptosis - genetics; Carrier Proteins - metabolism; Cell Cycle Proteins - metabolism; Cells, Cultured; Cercopithecus aethiops; Dynactin Complex; Embryo, Mammalian; Female; Green Fluorescent Proteins - genetics; Humans; Male; Medicine; Medicine & Public Health; Microscopy, Electron, Transmission; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Microtubules - metabolism; Motor Neurons - metabolism; Motor Neurons - pathology; Motor Neurons - ultrastructure; Mutation - genetics; Neurology; Neurology and Preclinical Neurological Studies - Original Article; Neurosciences; Parkinsonian Disorders - genetics; Parkinsonian Disorders - pathology; Pregnancy; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Psychiatry; Rats; Rats, Sprague-Dawley; Retrospective Studies; Spinal Cord - cytology; Time Factors; Parkinsonism; ALS; Dynactin; MND; p150 subunit
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-012-0910-z

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.