ArticleGenes to cells : devoted to molecular & cellular mechanisms2022
An ALS-associated KIF5A mutant forms oligomers and aggregates and induces neuronal toxicity.
Article in Genes to cells : devoted to molecular & cellular mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.Journal of neurochemistry · 2026Review
- Consequences of the Novel ALS-AssociatedNeurology. Genetics · 2026Article
- KIF5A and ALS: a clinical and genetic description of a case series and review of literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Targeted plasma proteomics uncover proteins associated with KIF5A-linked SPG10 and ALS spectrum disorders.HGG advances · 2026Article
- Kinesins inOpen biology · 2025Review
- Entering the era of precision medicine to treat amyotrophic lateral sclerosis.Molecular neurodegeneration · 2025Review
- New variants and genotype-phenotype correlation inJournal of medical genetics · 2025Article
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- ALS Mutations Shift the Isoelectric Point of the KIF5A C Terminal Inducing Protein Aggregation and TDP-43 Mislocalization.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.Cell communication and signaling : CCS · 2025Review
- SLC-25A46 regulates mitochondrial fusion through the mitofusin protein FZO-1 and is essential for maintaining neuronal morphology.Journal of cell science · 2025Article
- Using ALS to understand profilin 1's diverse roles in cellular physiology.Cytoskeleton (Hoboken, N.J.) · 2025Review
- Research progress of kinesin family in neurological diseases.Frontiers in cellular neuroscience · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Regulatory Role of Long Noncoding RNAs LINC00449 in Hepatocellular Carcinoma Mechanism and Prognosis Via Sponge miR-329-3p/KIF5A Axis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2024Article
- Axonopathy Underlying Amyotrophic Lateral Sclerosis: Unraveling Complex Pathways and Therapeutic Insights.Neuroscience bulletin · 2024Review
- Altered molecular and cellular mechanisms in KIF5A-associated neurodegenerative or neurodevelopmental disorders.Cell death & disease · 2024Article
- KIF5A regulates axonal repair and time-dependent axonal transport of SFPQ granules and mitochondria in human motor neurons.bioRxiv : the preprint server for biology · 2024Article
- KIF18B: an important role in signaling pathways and a potential resistant target in tumor development.Discover oncology · 2024Review
- The ALS-associated KIF5A P986L variant is not pathogenic for Drosophila motoneurons.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
Abstract
KIF5A is a kinesin superfamily motor protein that transports various cargos in neurons. Mutations in Kif5a cause familial amyotrophic lateral sclerosis (ALS). These ALS mutations are in the intron of Kif5a and induce mis-splicing of KIF5A mRNA, leading to splicing out of exon 27, which in human KIF5A encodes the cargo-binding tail domain of KIF5A. Therefore, it has been suggested that ALS is caused by loss of function of KIF5A. However, the precise mechanisms regarding how mutations in KIF5A cause ALS remain unclear. Here, we show that an ALS-associated mutant of KIF5A, KIF5A(Δexon27), is predisposed to form oligomers and aggregates in cultured mouse cell lines. Interestingly, purified KIF5A(Δexon27) oligomers showed more active movement on microtubules than wild-type KIF5A in vitro. Purified KIF5A(∆exon27) was prone to form aggregates in vitro. Moreover, KIF5A(Δexon27)-expressing Caenorhabditis elegans neurons showed morphological defects. These data collectively suggest that ALS-associated mutations of KIF5A are toxic gain-of-function mutations rather than simple loss-of-function mutations.
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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.