ArticleThe Journal of biological chemistry2010
Neurodegenerative mutation in cytoplasmic dynein alters its organization and dynein-dynactin and dynein-kinesin interactions.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Impaired dynein function preserves spinal interneuron survival and positioning in an ALS-like mouse model.PloS one · 2026Article
- Association of variants in the KIF1A gene with amyotrophic lateral sclerosis.Translational neurodegeneration · 2022Article
- A mathematical understanding of how cytoplasmic dynein walks on microtubules.Royal Society open science · 2018Article
- Ellagic acid attenuates arsenic induced neuro-inflammation and mitochondrial dysfunction associated apoptosis.Toxicology reports · 2018Article
- Neurobiology of axonal transport defects in motor neuron diseases: Opportunities for translational research?Neurobiology of disease · 2017Review
- DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Dync1h1 Mutation Causes Proprioceptive Sensory Neuron Loss and Impaired Retrograde Axonal Transport of Dorsal Root Ganglion Neurons.CNS neuroscience & therapeutics · 2016Article
- Mutation screen reveals novel variants and expands the phenotypes associated with DYNC1H1.Journal of neurology · 2015Article
- Analysis of dynein intermediate chains, light intermediate chains and light chains in a cohort of hereditary peripheral neuropathies.Neurogenetics · 2014Article
- Oatp1a1 requires PDZK1 to traffic to the plasma membrane by selective recruitment of microtubule-based motor proteins.Drug metabolism and disposition: the biological fate of chemicals · 2014Article
- Cytoplasmic dynein heavy chain: the servant of many masters.Trends in neurosciences · 2013Review
- The yeast dynein Dyn2-Pac11 complex is a dynein dimerization/processivity factor: structural and single-molecule characterization.Molecular biology of the cell · 2013Article
- Identification of a novel site in the tail of dynein heavy chain important for dynein function in vivo.The Journal of biological chemistry · 2013Article
- A mouse neurodegenerative dynein heavy chain mutation alters dynein motility and localization in Neurospora crassa.Cytoskeleton (Hoboken, N.J.) · 2012Article
- A novel phenotype for the dynein heavy chain mutation Loa: altered dendritic morphology, organelle density, and reduced numbers of trigeminal motoneurons.The Journal of comparative neurology · 2012Article
- A mutation in the dynein heavy chain gene compensates for energy deficit of mutant SOD1 mice and increases potentially neuroprotective IGF-1.Molecular neurodegeneration · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
A single amino acid change, F580Y (Legs at odd angles (Loa), Dync1h1(Loa)), in the highly conserved and overlapping homodimerization, intermediate chain, and light intermediate chain binding domain of the cytoplasmic dynein heavy chain can cause severe motor and sensory neuron loss in mice. The mechanism by which the Loa mutation impairs the neuron-specific functions of dynein is not understood. To elucidate the underlying molecular mechanisms of neurodegeneration arising from this mutation, we applied a cohort of biochemical methods combined with in vivo assays to systemically study the effects of the mutation on the assembly of dynein and its interaction with dynactin. We found that the Loa mutation in the heavy chain leads to increased affinity of this subunit of cytoplasmic dynein to light intermediate and a population of intermediate chains and a suppressed association of dynactin to dynein. These data suggest that the Loa mutation drives the assembly of cytoplasmic dynein toward a complex with lower affinity to dynactin and thus impairing transport of cargos that tether to the complex via dynactin. In addition, we detected up-regulation of kinesin light chain 1 (KLC1) and its increased association with dynein but reduced microtubule-associated KLC1 in the Loa samples. We provide a model describing how up-regulation of KLC1 and its interaction with cytoplasmic dynein in Loa could play a regulatory role in restoring the retrograde and anterograde transport in the Loa neurons.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.