ArticleProceedings of the National Academy of Sciences of the United States of America2015
Cytoplasmic dynein regulates its attachment to microtubules via nucleotide state-switched mechanosensing at multiple AAA domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 125 citations in OpenAlex.
- Many dynein teams collectively generate high forces during the transport of large organelles.Biophysical journal · 2026Article
- A nucleotide code governs Lis1's ability to relieve dynein autoinhibition.Nature chemical biology · 2026Article
- Adaptor-mediated recruitment of three dyneins to dynactin enhances force generation.Nature cell biology · 2026Article
- The mechanochemical cycle of reactive full-length human dynein 1.Nature structural & molecular biology · 2025Article
- Nanometer-resolution tracking of single cargo reveals dynein motor mechanisms.Nature chemical biology · 2025Article
- FAIR data for optical tweezers experiments.Biophysical journal · 2025Review
- MINFLUX reveals dynein stepping in live neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lis1 slows force-induced detachment of cytoplasmic dynein from microtubules.Nature chemical biology · 2024Article
- Wave-like oscillations of clamped microtubules driven by collective dynein transport.Biophysical journal · 2024Article
- Review
- Kindlin stabilizes the talin·integrin bond under mechanical load by generating an ideal bond.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Measurements of the Force-Dependent Detachment Rates of Cytoplasmic Dynein from Microtubules.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- AAA + ATPase Thorase inhibits mTOR signaling through the disassembly of the mTOR complex 1.Nature communications · 2022Article
- Calculating the force-dependent unbinding rate of biological macromolecular bonds from force-ramp optical trapping assays.Scientific reports · 2022Article
- Single-Molecule Studies on the Motion and Force Generation of the Kinesin-3 Motor KIF1A.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Dynein activation in vivo is regulated by the nucleotide states of its AAA3 domain.Current biology : CB · 2021Article
- Targeting allostery in the Dynein motor domain with small molecule inhibitors.Cell chemical biology · 2021Article
- Cytoplasmic factories for axonemal dynein assembly.Journal of cell science · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Cytoplasmic dynein is a homodimeric microtubule (MT) motor protein responsible for most MT minus-end-directed motility. Dynein contains four AAA+ ATPases (AAA: ATPase associated with various cellular activities) per motor domain (AAA1-4). The main site of ATP hydrolysis, AAA1, is the only site considered by most dynein motility models. However, it remains unclear how ATPase activity and MT binding are coordinated within and between dynein's motor domains. Using optical tweezers, we characterize the MT-binding strength of recombinant dynein monomers as a function of mechanical tension and nucleotide state. Dynein responds anisotropically to tension, binding tighter to MTs when pulled toward the MT plus end. We provide evidence that this behavior results from an asymmetrical bond that acts as a slip bond under forward tension and a slip-ideal bond under backward tension. ATP weakens MT binding and reduces bond strength anisotropy, and unexpectedly, so does ADP. Using nucleotide binding and hydrolysis mutants, we show that, although ATP exerts its effects via binding AAA1, ADP effects are mediated by AAA3. Finally, we demonstrate "gating" of AAA1 function by AAA3. When tension is absent or applied via dynein's C terminus, ATP binding to AAA1 induces MT release only if AAA3 is in the posthydrolysis state. However, when tension is applied to the linker, ATP binding to AAA3 is sufficient to "open" the gate. These results elucidate the mechanisms of dynein-MT interactions, identify regulatory roles for AAA3, and help define the interplay between mechanical tension and nucleotide state in regulating dynein motility.
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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.