Cited by 213Microtubule and mitosis dynamicsCancer Treatment and PharmacologyAlzheimer's disease research and treatments

Competition between microtubule-associated proteins directs motor transport

Open access
Monroy, Brigette Y., Sawyer, Danielle L., Ackermann, Bryce E., Borden, Melissa M., Tan, Tracy C., Ori-McKenney, Kassandra M.·2018·Nature Communications

Published version of a preprint

Abstract

Within cells, motor and non-motor microtubule-associated proteins (MAPs) simultaneously converge on the microtubule. How the binding activities of non-motor MAPs are coordinated and how they contribute to the balance and distribution of motor transport is unknown. Here, we examine the relationship between MAP7 and tau owing to their antagonistic roles in vivo. We find that MAP7 and tau compete for binding to microtubules, and determine a mechanism by which MAP7 displaces tau from the lattice. MAP7 promotes kinesin-based transport in vivo and strongly recruits kinesin-1 to the microtubule in vitro, providing evidence for direct enhancement of motor motility by a MAP. Both MAP7 and tau strongly inhibit kinesin-3 and have no effect on cytoplasmic dynein, demonstrating that MAPs differentially control distinct classes of motors. Overall, these results reveal a general principle for how MAP competition dictates access to the microtubule to determine the correct distribution and balance of motor activity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-018-03909-2

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • MAP7 competes with tau for lattice occupancy and has been shown to enhance kinesin-1 motility while inhibiting kinesin-3.

    “MAP7 competes with tau for lattice occupancy and has been shown to enhance kinesin-1 motility while inhibiting kinesin-3”
  • Envelope formation is sensitive to the intramolecular lattice spacing between α and β tubulin.

    “Envelope formation is sensitive to the intramolecular lattice spacing between α and β tubulin.”

    From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Monroy et al., 2018

    The Results section discusses MAP7 and tau competing for binding on the microtubule lattice, but does not address envelope formation or spacing between α- and β-tubulin. Searches for those terms and their paraphrases found no passage supporting the claim; page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured
  • Tau does not form envelopes on GMPCPP-polymerized microtubules, but readily forms envelopes on compacted GDP-lattices or reversibly expanded taxol-lattices.

    “Tau does not form envelopes on GMPCPP-polymerized microtubules, which are irreversibly expanded, mimicking the GTP-state, but readily forms envelopes on compacted GDP-lattices or reversibly expanded taxol-lattices”

    From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Monroy et al., 2018

    The Results section (‘MAP7 and tau exhibit overlapping localization patterns’; page unavailable) reports tau binding to taxol-stabilized microtubules, but does not establish envelope formation. Searches for ‘envelopes,’ ‘GMPCPP,’ and compacted GDP lattices found no passage comparing envelope formation across those lattice states. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 43

  1. [1]Harms MB Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy Neurology 2012 78 1714 1720 10.1212/WNL.0b013e3182556c05 22459677 PMC3359582 · DOI
  2. [2]Chevalier-Larsen E Holzbaur EL Axonal transport and neurodegenerative disease Biochim. Biophys. Acta 2006 1762 1094 1108 10.1016/j.bbadis.2006.04.002 16730956 · DOI
  3. [3]Ebneth A Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease J. Cell Biol. 1998 143 777 794 10.1083/jcb.143.3.777 9813097 PMC2148132 · DOI · Paper page
  4. [4]Semenova I Regulation of microtubule-based transport by MAP4 Mol. Biol. Cell 2014 25 3119 3132 10.1091/mbc.E14-01-0022 25143402 PMC4196864 · DOI · Paper page
  5. [6]Subramanian R Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein Cell 2010 142 433 443 10.1016/j.cell.2010.07.012 20691902 PMC2966277 · DOI
  6. [8]Trinczek B Ebneth A Mandelkow EM Mandelkow E Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles J. Cell Sci. 1999 112 2355 2367 10381391
  7. [9]Vershinin M Carter BC Razafsky DS King SJ Gross SP Multiple-motor based transport and its regulation by Tau Proc. Natl. Acad. Sci. USA 2007 104 87 92 10.1073/pnas.0607919104 17190808 PMC1765483 · DOI · Paper page
  8. [11]Stern JL Lessard DV Hoeprich GJ Morfini GA Berger CL Phosphoregulation of Tau modulates inhibition of kinesin-1 motility Mol. Biol. Cell 2017 28 1079 1087 10.1091/mbc.E16-10-0728 28251926 PMC5391184 · DOI · Paper page
  9. [12]Yu W The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches Mol. Biol. Cell 2008 19 1485 1498 10.1091/mbc.E07-09-0878 18234839 PMC2291400 · DOI
  10. [13]Tymanskyj SR Yang B Falnikar A Lepore AC Ma L MAP7 regulates axon collateral branch development in dorsal root Ganglion neurons J. Neurosci. 2017 37 1648 1661 10.1523/JNEUROSCI.3260-16.2017 28069923 PMC5299575 · DOI
  11. [14]Bulinski JC Bossler A Purification and characterization of ensconsin, a novel microtubule stabilizing protein J. Cell. Sci. 1994 107 2839 2849 7876351
  12. [15]Masson D Kreis TE Identification and molecular characterization of E-MAP-115, a novel microtubule-associated protein predominantly expressed in epithelial cells J. Cell Biol. 1993 123 357 371 10.1083/jcb.123.2.357 8408219 PMC2119845 · DOI
  13. [16]Barlan K Lu W Gelfand VI The microtubule-binding protein ensconsin is an essential cofactor of kinesin-1 Curr. Biol. 2013 23 317 322 10.1016/j.cub.2013.01.008 23394833 PMC3580027 · DOI
  14. [17]Metzger T MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function Nature 2012 484 120 124 10.1038/nature10914 22425998 PMC3321085 · DOI
  15. [18]Sung HH Drosophila ensconsin promotes productive recruitment of Kinesin-1 to microtubules Dev. Cell 2008 15 866 876 10.1016/j.devcel.2008.10.006 19081075 · DOI
  16. [19]Mandell JW Banker GA A spatial gradient of tau protein phosphorylation in nascent axons J. Neurosci. 1996 16 5727 5740 10.1523/JNEUROSCI.16-18-05727.1996 8795628 PMC6578967 · DOI
  17. [20]Drewes G Microtubule-associated protein/microtubule affinity-regulating kinase (p110mark). A novel protein kinase that regulates tau-microtubule interactions and dynamic instability by phosphorylation at the Alzheimer-specific site serine 262 J. Biol. Chem. 1995 270 7679 7688 10.1074/jbc.270.13.7679 7706316 · DOI · Paper page
  18. [21]Ackmann M Wiech H Mandelkow E Nonsaturable binding indicates clustering of tau on the microtubule surface in a paired helical filament-like conformation J. Biol. Chem. 2000 275 30335 30343 10.1074/jbc.M002590200 10869348 · DOI
  19. [22]Duan AR Goodson HV Taxol-stabilized microtubules promote the formation of filaments from unmodified full-length Tau in vitro Mol. Biol. Cell 2012 23 4796 4806 10.1091/mbc.E12-05-0374 23087208 PMC3521687 · DOI
  20. [23]Bulinski JC Odde DJ Howell BJ Salmon TD Waterman-Storer CM Rapid dynamics of the microtubule binding of ensconsin in vivo J. Cell Sci. 2001 114 3885 3897 11719555
  21. [24]Faire K E-MAP-115 (ensconsin) associates dynamically with microtubules in vivo and is not a physiological modulator of microtubule dynamics J. Cell Sci. 1999 112 4243 4255 10564643
  22. [25]Samsonov A Yu JZ Rasenick M Popov SV Tau interaction with microtubules in vivo J. Cell Sci. 2004 117 6129 6141 10.1242/jcs.01531 15564376 · DOI · Paper page
  23. [26]Butner KA Kirschner MW Tau protein binds to microtubules through a flexible array of distributed weak sites J. Cell Biol. 1991 115 717 730 10.1083/jcb.115.3.717 1918161 PMC2289193 · DOI · Paper page
  24. [27]Zheng Y Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons Nat. Cell Biol. 2008 10 1172 1180 10.1038/ncb1777 18758451 PMC2588425 · DOI
  25. [28]Zhou W GM130 is required for compartmental organization of dendritic golgi outposts Curr. Biol. 2014 24 1227 1233 10.1016/j.cub.2014.04.008 24835455 PMC4047983 · DOI
  26. [29]Ye B Growing dendrites and axons differ in their reliance on the secretory pathway Cell 2007 130 717 729 10.1016/j.cell.2007.06.032 17719548 PMC2020851 · DOI
  27. [30]Ori-McKenney KM Jan LY Jan YN Golgi outposts shape dendrite morphology by functioning as sites of acentrosomal microtubule nucleation in neurons Neuron 2012 76 921 930 10.1016/j.neuron.2012.10.008 23217741 PMC3523279 · DOI
  28. [31]Stone MC Roegiers F Rolls MM Microtubules have opposite orientation in axons and dendrites of Drosophila neurons Mol. Biol. Cell 2008 19 4122 4129 10.1091/mbc.E07-10-1079 18667536 PMC2555934 · DOI
  29. [32]Yalgin C Centrosomin represses dendrite branching by orienting microtubule nucleation Nat. Neurosci. 2015 18 1437 1445 10.1038/nn.4099 26322925 · DOI
  30. [33]Satoh D Spatial control of branching within dendritic arbors by dynein-dependent transport of Rab5-endosomes Nat. Cell Biol. 2008 10 1164 1171 10.1038/ncb1776 18758452 · DOI
  31. [34]Gallaud E Ensconsin/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells J. Cell Biol. 2014 204 1111 1121 10.1083/jcb.201311094 24687279 PMC3971751 · DOI
  32. [35]Thorn KS Ubersax JA Vale RD Engineering the processive run length of the kinesin motor J. Cell Biol. 2000 151 1093 1100 10.1083/jcb.151.5.1093 11086010 PMC2174356 · DOI
  33. [36]Lipka J Kapitein LC Jaworski J Hoogenraad CC Microtubule-binding protein doublecortin-like kinase 1 (DCLK1) guides kinesin-3-mediated cargo transport to dendrites EMBO J. 2016 35 302 318 10.15252/embj.201592929 26758546 PMC4741305 · DOI
  34. [37]McKenney RJ Huynh W Tanenbaum ME Bhabha G Vale RD Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes Science 2014 345 337 341 10.1126/science.1254198 25035494 PMC4224444 · DOI
  35. [38]Gustke N The Alzheimer-like phosphorylation of tau protein reduces microtubule binding and involves Ser-Pro and Thr-Pro motifs FEBS Lett. 1992 307 199 205 10.1016/0014-5793(92)80767-B 1644173 · DOI
  36. [39]Chapin SJ Bulinski JC Non-neuronal 210 x 10(3) Mr microtubule-associated protein (MAP4) contains a domain homologous to the microtubule-binding domains of neuronal MAP2 and tau J. Cell. Sci. 1991 98 27 36 1905296
  37. [40]Yu I Garnham CP Roll-Mecak A Writing and reading the tubulin code J. Biol. Chem. 2015 290 17163 17172 10.1074/jbc.R115.637447 25957412 PMC4498056 · DOI
  38. [41]Verhey KJ Gaertig J The tubulin code Cell Cycle 2007 6 2152 2160 10.4161/cc.6.17.4633 17786050 · DOI · Paper page
  39. [42]Castoldi M Popov AV Purification of brain tubulin through two cycles of polymerization-depolymerization in a high-molarity buffer Protein Expr. Purif. 2003 32 83 88 10.1016/S1046-5928(03)00218-3 14680943 · DOI
  40. [43]Edelstein, A., et al. Computer control of microscopes using µManager. Chapter 14, Unit14.20 (2010). PMC3065365 20890901
  41. [44]Lee SB Bagley JA Lee HY Jan LY Jan YN Pathogenic polyglutamine proteins cause dendrite defects associated with specific actin cytoskeletal alterations in Drosophila Proc. Natl. Acad. Sci. USA 2011 108 16795 16800 10.1073/pnas.1113573108 21930920 PMC3189048 · DOI
  42. [45]Longair MH Baker DA Armstrong JD Simple Neurite Tracer: open source software for reconstruction, visualization and analysis of neuronal processes Bioinformatics 2011 27 2453 2454 10.1093/bioinformatics/btr390 21727141 · DOI
  43. [46]Ori-McKenney KM Xu J Gross SP Vallee RB A cytoplasmic dynein tail mutation impairs motor processivity Nat. Cell Biol. 2010 12 1228 1234 10.1038/ncb2127 21102439 PMC3385513 · DOI

Cited by

Sorted by citations

Authors
Monroy, B. Y., Sawyer, D. L., Ackermann, B. E., Borden, M. M., Tan, T. C., & Ori-McKenney, K. M.
Affiliations
University of California, Davis (US)
Corresponding author
Ori-McKenney, Kassandra M.
Venue
Nature Communications
Published
2018-04-16
Volume
9
Issue
1
Pages
1487-1487
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2953010568
Cited by
213
References
3
Citations by year
2026: 19 · 2025: 17 · 2024: 19 · 2023: 37 · 2022: 25 · 2021: 30 · 2020: 35 · 2019: 22 · 2018: 8 · 2017: 1
FWCI
13.13
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Science Foundation (1650042)
  • March of Dimes Foundation
  • National Institutes of Health (1650042)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R00HD080981)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
microtubule-associated proteins, MAP7, tau protein, kinesin-1, kinesin-3, cytoplasmic dynein, road transport, microtubule lattice
MeSH terms
Animals, Binding, Competitive, Biological Transport, Drosophila melanogaster, Dyneins, Humans, Microtubule-Associated Proteins, Microtubules, Neurons, Protein Binding, Swine, Tubulin, Gene Expression, Kinesins, tau Proteins, Mice, Primary Cell Culture

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review