title: The dynactin p150 subunit: cell biology studies of sequence changes found in ALS/MND and Parkinsonian syndromes.
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.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University, Albert-Einstein Allee 11, 89081 Ulm, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Stockmann
authors.forename: Marie
authors.initials: M
authors.lastname: Meyer-Ohlendorf
authors.forename: Kevin
authors.initials: K
authors.lastname: Achberger
authors.forename: Stefan
authors.initials: S
authors.lastname: Putz
authors.forename: Maria
authors.initials: M
authors.lastname: Demestre
authors.forename: Haishan
authors.initials: H
authors.lastname: Yin
authors.forename: Corinna
authors.initials: C
authors.lastname: Hendrich
authors.forename: Leonhard
authors.initials: L
authors.lastname: Linta
authors.forename: Jutta
authors.initials: J
authors.lastname: Heinrich
authors.forename: Cornelia
authors.initials: C
authors.lastname: Brunner
authors.forename: Christian
authors.initials: C
authors.lastname: Proepper
authors.forename: Georges F
authors.initials: GF
authors.lastname: Kuh
authors.forename: Bernd
authors.initials: B
authors.lastname: Baumann
authors.forename: Torben
authors.initials: T
authors.lastname: Langer
authors.forename: Birgit
authors.initials: B
authors.lastname: Schwalenstöcker
authors.forename: Kerstin E
authors.initials: KE
authors.lastname: Braunstein
authors.forename: Christine
authors.initials: C
authors.lastname: von Arnim
authors.forename: Stephan
authors.initials: S
authors.lastname: Schneuwly
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.forename: Philip C
authors.initials: PC
authors.lastname: Wong
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D000072159:Dynactin Complex; D004622:Embryo, Mammalian; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology*; D011247:Pregnancy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012189:Retrospective Studies; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C107792:UBQLN1 protein, human; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease