ArticleProceedings of the National Academy of Sciences of the United States of America2016
Role of kinesin-1-based microtubule sliding in Drosophila nervous system development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 91 citations in OpenAlex.
- Microtubules in Spinal Cord Injury: From Cytoskeletal Dysregulation to Therapeutic Regeneration.Journal of neurochemistry · 2026Review
- Motor Protein Disruption Critically Alters Organelle Trafficking and Excitation-Contraction Coupling.eNeuro · 2026Article
- Identification of a cytosol-to-nucleus feedback loop that regulates neuronal microtubule nucleation.The Journal of cell biology · 2026Article
- Motor-Assisted Co-Migration of Intracellular Organelles and Microtubules as a Mechanism for Directed Cargo Transport.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Katanin-mediated severing generates microtubules during neurite outgrowth.Research square · 2026Article
- Non-transport functions of motor proteins in corticogenesis.Frontiers in cell and developmental biology · 2026Review
- Roles of molecular motors in insulin-secreting beta cells.Current opinion in cell biology · 2025Review
- Inactivation of microtubule organizing center function of the centrosome is required for neuronal development and centriole elimination.bioRxiv : the preprint server for biology · 2025Article
- Polarity reversal of stable microtubules during neuronal development.Journal of cell science · 2025Article
- Article
- Regulation of Axonal Microtubule Polarity Orientation in Different Kinds of Neurons.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- 'Mitotic' kinesin-5 is a dynamic brake for axonal growth in Drosophila.Development (Cambridge, England) · 2025Article
- Mechanism and regulation of kinesin motors.Nature reviews. Molecular cell biology · 2025Review
- Tubulin CFEOM mutations both inhibit or activate kinesin motor activity.Molecular biology of the cell · 2024Article
- UNC-116 and UNC-16 function with the NEKL-3 kinase to promote axon targeting.Development (Cambridge, England) · 2023Article
- Presynaptic Precursor Vesicles-Cargo, Biogenesis, and Kinesin-Based Transport across Species.Cells · 2023Review
- Control of motor landing and processivity by the CAP-Gly domain in the KIF13B tail.Nature communications · 2023Article
- The role of mechanics in axonal stability and development.Seminars in cell & developmental biology · 2023Review
- Kinesin-1 autoinhibition facilitates the initiation of dynein cargo transport.The Journal of cell biology · 2023Article
- Go with the flow - bulk transport by molecular motors.Journal of cell science · 2023Review
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
The plus-end microtubule (MT) motor kinesin-1 is essential for normal development, with key roles in the nervous system. Kinesin-1 drives axonal transport of membrane cargoes to fulfill the metabolic needs of neurons and maintain synapses. We have previously demonstrated that kinesin-1, in addition to its well-established role in organelle transport, can drive MT-MT sliding by transporting "cargo" MTs along "track" MTs, resulting in dramatic cell shape changes. The mechanism and physiological relevance of this MT sliding are unclear. In addition to its motor domain, kinesin-1 contains a second MT-binding site, located at the C terminus of the heavy chain. Here, we mutated this C-terminal MT-binding site such that the ability of kinesin-1 to slide MTs is significantly compromised, whereas cargo transport is unaffected. We introduced this mutation into the genomic locus of kinesin-1 heavy chain (KHC), generating the Khc(mutA) allele. Khc(mutA) neurons displayed significant MT sliding defects while maintaining normal transport of many cargoes. Using this mutant, we demonstrated that MT sliding is required for axon and dendrite outgrowth in vivo. Consistent with these results, Khc(mutA) flies displayed severe locomotion and viability defects. To test the role of MT sliding further, we engineered a chimeric motor that actively slides MTs but cannot transport organelles. Activation of MT sliding in Khc(mutA) neurons using this chimeric motor rescued axon outgrowth in cultured neurons and in vivo, firmly establishing the role of sliding in axon outgrowth. These results demonstrate that MT sliding by kinesin-1 is an essential biological phenomenon required for neuronal morphogenesis and normal nervous system development.
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