Multiple-motor based transport and its regulation by Tau
Open accessAbstract
Motor-based intracellular transport and its regulation are crucial to the functioning of a cell. Disruption of transport is linked to Alzheimer's and other neurodegenerative diseases. However, many fundamental aspects of transport are poorly understood. An important issue is how cells achieve and regulate efficient long-distance transport. Mounting evidence suggests that many in vivo cargoes are transported along microtubules by more than one motor, but we do not know how multiple motors work together or can be regulated. Here we first show that multiple kinesin motors, working in conjunction, can achieve very long distance transport and apply significantly larger forces without the need of additional factors. We then demonstrate in vitro that the important microtubule-associated protein, tau, regulates the number of engaged kinesin motors per cargo via its local concentration on microtubules. This function of tau provides a previously unappreciated mechanism to regulate transport. By reducing motor reattachment rates, tau affects cargo travel distance, motive force, and cargo dispersal. We also show that different isoforms of tau, at concentrations similar to those in cells, have dramatically different potency. These results provide a well defined mechanism for how altered tau isoform levels could impair transport and thereby lead to neurodegeneration without the need of any other pathway.
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Some motors, such as kinesin-1 and kinesin-3, are strongly inhibited by tau in an isoform- and lattice-dependent manner, while kinesin-2 and dynein can more effectively navigate tau-decorated regions.
“While some motors, such as kinesin-1 and kinesin-3, are strongly inhibited by tau in an isoform- and lattice-dependent manner, others, like kinesin-2 and dynein, can more effectively navigate tau-decorated regions”
From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Vershinin et al., 2007
The Results and Discussion (page unavailable) show that tau inhibits transport by multiple kinesin-I motors, with a much stronger effect from 3RS than 4RL tau. The Materials and Methods (page unavailable) identify kinesin-I as the motor studied and say the preparation contained no dynein. The paper does not establish the claimed effects on kinesin-3 or kinesin-2, their relative ability to navigate tau-decorated regions, or dependence on lattice type. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTau acts as a selective barrier on microtubules to direct intracellular transport.
“Tau regulates the axonal cytoskeleton (Kanai et al., 1992; Chen et al., 1992; Panda et al., 2003; Rosenberg et al., 2008; Chung et al., 2015; Biswas and Kalil, 2018), and acts as a selective barrier on microtubules to direct intracellular transport”
From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Vershinin et al., 2007
The paper’s opening summary reports that tau on microtubules reduces kinesin reattachment and thereby regulates cargo travel distance and dispersal. The Results and Discussion demonstrate this effect in vitro, but do not establish that tau acts as a selective barrier that directs intracellular transport in cells. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe extent of tau's influence on motor proteins depends on the tau isoform and PTMs, the underlying microtubule lattice, and the intrinsic properties of the motors themselves.
“The extent of tau’s influence on motor proteins depends on several factors including (1) the tau isoform and PTMs, (2) the underlying microtubule lattice, and (3) the intrinsic properties of the motors themselves.”
From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Vershinin et al., 2007
The Results and Discussion (page not available) show that 3RS and 4RL tau differ substantially in their effects on kinesin transport, supporting the isoform part of the claim. The paper does not establish that tau’s effects depend on tau PTMs or the underlying microtubule lattice; its discussion of motor properties is limited to kinesin and differences between assay conditions, not a general dependence on motors’ intrinsic properties. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAxonal cargoes are transported by teams of motors with differing sensitivities to tau.
“Axonal cargoes are transported by teams of motors with differing sensitivities to tau, as we observed for kinesin-1 (KIF5C) and kinesin-3 (KIF1A) (Figure 3) and as shown previously”
From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Vershinin et al., 2007
The Results and Discussion (page unavailable) show that multiple kinesin motors can move a cargo and that tau regulates how many remain engaged. The experiments used the same type of motor in vitro; they do not establish that axonal cargoes are carried by teams of different motors with differing sensitivities to tau. The reported difference in potency is between tau isoforms, not motor types. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPrevious studies showed that tau differentially regulates motor proteins, with kinesin-1 and kinesin-3 being more sensitive to tau-mediated inhibition than kinesin-2 and dynein.
“Previous studies showed that tau differentially regulates motor proteins, with kinesin-1 and kinesin-3 being more sensitive to tau-mediated inhibition than kinesin-2 and dynein”
From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Vershinin et al., 2007
The Results and Discussion report that tau reduces kinesin’s motor-attachment rate and that different tau isoforms have different effects. They do not compare tau-mediated inhibition across kinesin-1, kinesin-2, kinesin-3, and dynein, so the claimed ranking of motor sensitivity is not supported by our copy. (LLM, conf=0.86)
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- Authors
- Vershinin, M., Carter, B. C., Razafsky, D. S., King, S. J., & Gross, S. P.
- Affiliations
- University of California, Irvine (US)
- University of Missouri–Kansas City (US)
- Corresponding author
- Gross, Steven P.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-01-02
- Volume
- 104
- Issue
- 1
- Pages
- 87-92
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1765483
- OpenAlex
- W2022214576
- Cited by
- 457
- References
- 2
- Citations by year
- 2026: 14 · 2025: 18 · 2024: 18 · 2023: 19 · 2022: 20 · 2021: 23 · 2020: 32 · 2019: 29 · 2018: 31 · 2017: 25 · 2016: 23 · 2015: 21 · 2014: 34 · 2013: 19 · 2012: 35
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM070676)
- National Institute of Neurological Disorders and Stroke (R01NS048501)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- intracellular transport, kinesin motors, tau protein, microtubules, motive force, tau isoforms, Alzheimer's disease, neurodegeneration, long-distance transport
- MeSH terms
- Humans, Microtubules, Kinesins, tau Proteins, Neurodegenerative Diseases, Protein Isoforms, Protein Transport
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