ArticleFrontiers in cellular neuroscience2016
KIF5C S176 Phosphorylation Regulates Microtubule Binding and Transport Efficiency in Mammalian Neurons.
Article in Frontiers in cellular neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Gene expression profiles in sporadic ALS fibroblasts define disease subtypes and the metabolic effects of the investigational drug EH301.Human molecular genetics · 2022Pooled it
- Traffic Jams in the Brain: How Kinesin Dysfunction Shapes Neurodevelopmental Disorders.Current issues in molecular biology · 2026Review
- Review
- Loss of PINK1 causes age-dependent mitochondrial trafficking deficits in nigrostriatal dopaminergic neurons via aberrant p38 MAPK activation.NPJ Parkinson's disease · 2026Article
- Mutant TDP-43 drives impairments in axonal transport and glycolysis in a mouse stem-cell-derived motor neuron model of amyotrophic lateral sclerosis (ALS).Cell death & disease · 2026Article
- Are Hippocampal Hypoperfusion and ATP Depletion Prime Movers in the Genesis of Alzheimer's Disease? A Review of Recent Pertinent Observations from Molecular Biology.International journal of molecular sciences · 2025Review
- Mechanism and regulation of kinesin motors.Nature reviews. Molecular cell biology · 2025Review
- F-box protein FBXB-65 regulates anterograde transport of the kinesin-3 motor UNC-104 through a PTM near its cargo-binding PH domain.Journal of cell science · 2024Article
- Unraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer's disease.Frontiers in cellular neuroscience · 2024Review
- A human proteogenomic-cellular framework identifies KIF5A as a modulator of astrocyte process integrity with relevance to ALS.Communications biology · 2023Article
- Disruption of axonal transport in neurodegeneration.The Journal of clinical investigation · 2023Review
- Glycogen synthase kinase 3β (GSK3β) and presenilin (PS) are key regulators of kinesin-1-mediated cargo motility within axons.Frontiers in cell and developmental biology · 2023Review
- Phosphoregulation of Kinesins Involved in Long-Range Intracellular Transport.Frontiers in cell and developmental biology · 2022Review
- Cytoskeleton and Associated Proteins: Pleiotropic JNK Substrates and Regulators.International journal of molecular sciences · 2021Review
- Normal levels of KIF5 but reduced KLC1 levels in both Alzheimer disease and Alzheimer disease in Down syndrome: evidence suggesting defects in anterograde transport.Alzheimer's research & therapy · 2021Article
- Identification of SNPs and Candidate Genes for Milk Production Ability in Yorkshire Pigs.Frontiers in genetics · 2021Article
- Review
- Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue.The Journal of cell biology · 2020Article
- Article
- Polyglutamylation of tubulin's C-terminal tail controls pausing and motility of kinesin-3 family member KIF1A.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
Increased phosphorylation of the KIF5 anterograde motor is associated with impaired axonal transport and neurodegeneration, but paradoxically also with normal transport, though the details are not fully defined. JNK phosphorylates KIF5C on S176 in the motor domain; a site that we show is phosphorylated in brain. Microtubule pelleting assays demonstrate that phosphomimetic KIF5C(1-560)(S176D) associates weakly with microtubules compared to KIF5C(1-560)(WT). Consistent with this, 50% of KIF5C(1-560)(S176D) shows diffuse movement in neurons. However, the remaining 50% remains microtubule bound and displays decreased pausing and increased bidirectional movement. The same directionality switching is observed with KIF5C(1-560)(WT) in the presence of an active JNK chimera, MKK7-JNK. Yet, in cargo trafficking assays where peroxisome cargo is bound, KIF5C(1-560)(S176D)-GFP-FRB transports normally to microtubule plus ends. We also find that JNK increases the ATP hydrolysis of KIF5C in vitro. These data suggest that phosphorylation of KIF5C-S176 primes the motor to either disengage entirely from microtubule tracks as previously observed in response to stress, or to display improved efficiency. The final outcome may depend on cargo load and motor ensembles.
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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.