ArticlePLoS genetics2012
Spastic paraplegia mutation N256S in the neuronal microtubule motor KIF5A disrupts axonal transport in a Drosophila HSP model.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Functional validation of the novel KIF5A p.R17Q VUS reveals defective axonal transport in iPSC-motoneurons from a SPG10 patient.Frontiers in genetics · 2026Article
- Wings of Discovery: UsingCells · 2025Review
- One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.Cell communication and signaling : CCS · 2025Review
- Loss of Fic causes progressive neurodegeneration in a Drosophila model of hereditary spastic paraplegia.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Hereditary spastic paraplegia: Novel insights into the pathogenesis and management.SAGE open medicine · 2024Review
- ALS-Associated KIF5A Mutation Causes Locomotor Deficits Associated with Cytoplasmic Inclusions, Alterations of Neuromuscular Junctions, and Motor Neuron Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Impaired motor unit recovery and maintenance in a knock-in mouse model of ALS-associated Kif5a variant.Neurobiology of disease · 2023Article
- Decoding hereditary spastic paraplegia pathogenicity through transcriptomic profiling.Zoological research · 2023Review
- A new model for fatty acid hydroxylase-associated neurodegeneration reveals mitochondrial and autophagy abnormalities.Frontiers in cell and developmental biology · 2022Article
- Temporal Cortex Microarray Analysis Revealed Impaired Ribosomal Biogenesis and Hyperactivity of the Glutamatergic System: An Early Signature of Asymptomatic Alzheimer's Disease.Frontiers in neuroscience · 2022Article
- A stop or go switch: glycogen synthase kinase 3β phosphorylation of the kinesin 1 motor domain at Ser314 halts motility without detaching from microtubules.Development (Cambridge, England) · 2021Article
- Autophagy inhibition rescues structural and functional defects caused by the loss of mitochondrial chaperoneAutophagy · 2021Article
- Review
- Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival.The Journal of cell biology · 2021Article
- Excess Rab4 rescues synaptic and behavioral dysfunction caused by defective HTT-Rab4 axonal transport in Huntington's disease.Acta neuropathologica communications · 2020Article
- Axonal transport and neurological disease.Nature reviews. Neurology · 2019Review
- Going Too Far Is the Same as Falling ShortFrontiers in cellular neuroscience · 2019Review
- A Systematic Review of Suggested Molecular Strata, Biomarkers and Their Tissue Sources in ALS.Frontiers in neurology · 2019Review
- The small G protein Arl8 contributes to lysosomal function and long-range axonal transport inBiology open · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hereditary spastic paraplegias (HSPs) comprise a group of genetically heterogeneous neurodegenerative disorders characterized by spastic weakness of the lower extremities. We have generated a Drosophila model for HSP type 10 (SPG10), caused by mutations in KIF5A. KIF5A encodes the heavy chain of kinesin-1, a neuronal microtubule motor. Our results imply that SPG10 is not caused by haploinsufficiency but by the loss of endogenous kinesin-1 function due to a selective dominant-negative action of mutant KIF5A on kinesin-1 complexes. We have not found any evidence for an additional, more generalized toxicity of mutant Kinesin heavy chain (Khc) or the affected kinesin-1 complexes. Ectopic expression of Drosophila Khc carrying a human SPG10-associated mutation (N256S) is sufficient to disturb axonal transport and to induce motoneuron disease in Drosophila. Neurofilaments, which have been recently implicated in SPG10 disease manifestation, are absent in arthropods. Impairments in the transport of kinesin-1 cargos different from neurofilaments are thus sufficient to cause HSP-like pathological changes such as axonal swellings, altered structure and function of synapses, behavioral deficits, and increased mortality.
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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.