ArticleThe Journal of biological chemistry2013
Motor domain phosphorylation modulates kinesin-1 transport.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
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- Patient stratification reveals the molecular basis of disease co-occurrences.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- The doublecortin-family kinase ZYG-8DCLK1 regulates microtubule dynamics and motor-driven forces to promote the stability of C. elegans acentrosomal spindles.PLoS genetics · 2024Article
- Modification of the neck-linker of KIF18A alters Microtubule subpopulation preference.Molecular biology of the cell · 2024Article
- Unraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer's disease.Frontiers in cellular neuroscience · 2024Review
- A kinesin-1 adaptor complex controls bimodal slow axonal transport of spectrin in Caenorhabditis elegans.Developmental cell · 2023Article
- 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
- 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
- The multifaceted role of kinases in amyotrophic lateral sclerosis: genetic, pathological and therapeutic implications.Brain : a journal of neurology · 2020Review
- Article
- Chemotherapy-Induced Peripheral Neuropathy and Changes in Cytoskeleton.International journal of molecular sciences · 2019Review
- Tau and Axonal Transport Misregulation in Tauopathies.Advances in experimental medicine and biology · 2019Review
- E-hooks provide guidance and a soft landing for the microtubule binding domain of dynein.Scientific reports · 2018Article
- JIP3 localises to exocytic vesicles and focal adhesions in the growth cones of differentiated PC12 cells.Molecular and cellular biochemistry · 2018Article
- A posttranslational modification of the mitotic kinesin Eg5 that enhances its mechanochemical coupling and alters its mitotic function.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Src family kinase phosphorylation of the motor domain of the human kinesin-5, Eg5.Cytoskeleton (Hoboken, N.J.) · 2017Article
- Regulation of motor proteins, axonal transport deficits and adult-onset neurodegenerative diseases.Neurobiology of disease · 2017Review
- Interrogating Emergent Transport Properties for Molecular Motor Ensembles: A Semi-analytical Approach.PLoS computational biology · 2016Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Disruptions in microtubule motor transport are associated with a variety of neurodegenerative diseases. Post-translational modification of the cargo-binding domain of the light and heavy chains of kinesin has been shown to regulate transport, but less is known about how modifications of the motor domain affect transport. Here we report on the effects of phosphorylation of a mammalian kinesin motor domain by the kinase JNK3 at a conserved serine residue (Ser-175 in the B isoform and Ser-176 in the A and C isoforms). Phosphorylation of this residue has been implicated in Huntington disease, but the mechanism by which Ser-175 phosphorylation affects transport is unclear. The ATPase, microtubule-binding affinity, and processivity are unchanged between a phosphomimetic S175D and a nonphosphorylatable S175A construct. However, we find that application of force differentiates between the two. Placement of negative charge at Ser-175, through phosphorylation or mutation, leads to a lower stall force and decreased velocity under a load of 1 piconewton or greater. Sedimentation velocity experiments also show that addition of a negative charge at Ser-175 favors the autoinhibited conformation of kinesin. These observations imply that when cargo is transported by both dynein and phosphorylated kinesin, a common occurrence in the cell, there may be a bias that favors motion toward the minus-end of microtubules. Such bias could be used to tune transport in healthy cells when properly regulated but contribute to a disease state when misregulated.
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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.