CoChat
Sign Up
Cited by 112Microtubule and mitosis dynamicsGenetic and Kidney Cyst DiseasesProtein Structure and Dynamics

Structural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7

Open access
Ferro, Luke S., Fang, Qianglin, Eshun-Wilson, Lisa, Fernandes, Jonathan, Jack, Amanda, Farrell, Daniel P., Golcuk, Mert, Huijben, Teun +5 more·2022·Science
DOI 10.1126/science.abf6154PMC PMC8985661
Open this paper in CoChat — free account

Abstract

Microtubule (MT)–associated protein 7 (MAP7) is a required cofactor for kinesin-1–driven transport of intracellular cargoes. Using cryo–electron microscopy and single–molecule imaging, we investigated how MAP7 binds MTs and facilitates kinesin-1 motility. The MT-binding domain (MTBD) of MAP7 bound MTs as an extended α helix between the protofilament ridge and the site of lateral contact. Unexpectedly, the MTBD partially overlapped with the binding site of kinesin-1 and inhibited its motility. However, by tethering kinesin-1 to the MT, the projection domain of MAP7 prevented dissociation of the motor and facilitated its binding to available neighboring sites. The inhibitory effect of the MTBD dominated as MTs became saturated with MAP7. Our results reveal biphasic regulation of kinesin-1 by MAP7 in the context of their competitive binding to MTs.

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 · 10.1126/science.abf6154

Cites

4 of 4 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?

  • Various microtubule-binding proteins have higher affinities for expanded or compacted lattices in vitro and can induce lattice expansion or compaction, respectively.

    “various microtubule-binding proteins have higher affinities for expanded or compacted lattices in vitro and can also induce lattice expansion or compaction, respectively (Ferro et al., 2022; Guedes-Dias et al., 2019; Peet et al., 2018; Shima et al., 2018; Watanabe et al., 2020; Zhang et al., 2017)”

    From StableMARK-decorated microtubules in cells have expanded lattices (2025) · cites this paper as Ferro et al., 2022

    The paper’s structural discussion (indexed as Abstract; page unavailable) describes where MAP7 binds on microtubules, and its motility experiments report MAP7 binding affinity. Neither addresses preferential binding to expanded versus compacted lattices or MAP7-induced lattice expansion or compaction. Searches for “expanded,” “compacted,” and lattice-spacing terms found no passage establishing the attributed point. (LLM, conf=0.74)

    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: 53

  1. [1]Bodakuntla S, Jijumon AS, Villablanca C, Gonzalez-Billault C, Janke C, Microtubule-Associated Proteins: Structuring the Cytoskeleton. Trends in Cell Biol 29, 804– 819 (2019). 31416684
  2. [2]Roll-Mecak A, The Tubulin Code in Microtubule Dynamics and Information Encoding. Developmental Cell 54, 7– 20 (2020). 32634400 PMC11042690
  3. [3]Gumy LF, MAP2 Defines a Pre-axonal Filtering Zone to Regulate KIF1- versus KIF5-Dependent Cargo Transport in Sensory Neurons. Neuron 94, 347– 362 (2017). 28426968
  4. [4]Ebneth A, Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer’s disease. JCB 143, 777– 794 (1998). 9813097 PMC2148132
  5. [5]Ishihara T, Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron 24, 751– 762 (1999). 10595524
  6. [6]Vossel KA, Tau reduction prevents Abeta-induced defects in axonal transport. Science 330, 198 (2010). 20829454 PMC3024010
  7. [7]Barlan K, Lu W, Gelfand VI, The microtubule-binding protein ensconsin is an essential cofactor of kinesin-1. Current Biol 23, 317– 322 (2013). PMC3580027 23394833
  8. [8]Tymanskyj SR, Yang BH, Verhey KJ, Ma L, MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport. eLife 7, e36374 (2018). 30132755 PMC6133550
  9. [9]Hooikaas PJ, MAP7 family proteins regulate kinesin-1 recruitment and activation. JCB 218, 1298– 1318 (2019). 30770434 PMC6446838
  10. [10]Monroy BY, Competition between microtubule-associated proteins directs motor transport. Nature Comm 9, 1487 (2018). PMC5902456 29662074
  11. [13]Kellogg EH, Near-atomic model of microtubule-tau interactions. Science 360, 1242– 1246 (2018). 29748322 PMC6225777
  12. [14]Shigematsu H, Structural insight into microtubule stabilization and kinesin inhibition by Tau family MAPs. JCB 217, 4155– 4163 (2018). 30275105 PMC6279373
  13. [15]Song YF, High-Resolution Comparative Modeling with RosettaCM. Structure 21, 1735– 1742 (2013). 24035711 PMC3811137
  14. [16]Canty JT, Tan R, Kusakci E, Fernandes J, Yildiz A, Structure and Mechanics of Dynein Motors. Ann Rev of Biophysics 50, 549– 574 (2021). PMC8592121 33957056
  15. [17]Verhey KJ, Kaul N, Soppina V, Kinesin assembly and movement in cells. Ann Rev of Biophysics 40, 267– 288 (2011). 21332353
  16. [18]Chaudhary AR, MAP7 regulates organelle transport by recruiting kinesin-1 to microtubules. JBC 294, 10160– 10171 (2019). PMC6664170 31085585
  17. [19]Valenstein ML, Roll-Mecak A, Graded Control of Microtubule Severing by Tubulin Glutamylation. Cell 164, 911– 921 (2016). 26875866 PMC6459029
  18. [20]Gigant B, Structure of a kinesin-tubulin complex and implications for kinesin motility. NSMB 20, 1001– 1007 (2013). 23872990
  19. [21]Liu JS, Molecular basis for specific regulation of neuronal kinesin-3 motors by doublecortin family proteins. Molecular Cell 47, 707– 721 (2012). 22857951 PMC3549492
  20. [24]Schneider R, Korten T, Walter WJ, Diez S, Kinesin-1 motors can circumvent permanent roadblocks by side-shifting to neighboring protofilaments. Biophys J 108, 2249– 2257 (2015). 25954882 PMC4423065
  21. [25]Sung HH, Drosophila ensconsin promotes productive recruitment of Kinesin-1 to microtubules. Developmental Cell 15, 866– 876 (2008). 19081075
  22. [26]Gallaud E, Ensconsin/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells. JCB 204, 1111– 1121 (2014). 24687279 PMC3971751
  23. [27]Yin J, Genetically encoded short peptide tag for versatile protein labeling by Sfp phosphopantetheinyl transferase. PNAS 102, 15815– 15820 (2005). 16236721 PMC1276090
  24. [28]Schlager MA, Hoang HT, Urnavicius L, Bullock SL, Carter AP, In vitro reconstitution of a highly processive recombinant human dynein complex. The EMBO J 33, 1855– 1868 (2014). 24986880 PMC4158905
  25. [29]Ferro LS, Can S, Turner MA, ElShenawy MM, Yildiz A, Kinesin and dynein use distinct mechanisms to bypass obstacles. eLife 8, e48629 (2019). 31498080 PMC6783262
  26. [30]Zhang K, Cryo-EM Reveals How Human Cytoplasmic Dynein Is Auto-inhibited and Activated. Cell 169, 1303– 1314 (2017). 28602352 PMC5473941
  27. [31]Kellogg EH, Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures. J Mol Biol 429, 633– 646 (2017). 28104363 PMC5325780
  28. [32]West LM, Northcote PT, Battershill CN, Peloruside A: a potent cytotoxic macrolide isolated from the new zealand marine sponge Mycale sp. J Org Chem 65, 445– 449 (2000). 10813954
  29. [33]Eshun-Wilson L, Effects of alpha-tubulin acetylation on microtubule structure and stability. PNAS 116, 10366– 10371 (2019). 31072936 PMC6535015
  30. [34]Zhang R, Alushin GM, Brown A, Nogales E, Mechanistic Origin of Microtubule Dynamic Instability and Its Modulation by EB Proteins. Cell 162, 849– 859 (2015). 26234155 PMC4537847
  31. [35]Mastronarde DN, Automated electron microscope tomography using robust prediction of specimen movements. J Struct Biol 152, 36– 51 (2005). 16182563
  32. [36]Zheng SQ, MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nature Methods 14, 331– 332 (2017). 28250466 PMC5494038
  33. [37]Zhang K, Gctf: Real-time CTF determination and correction. J Struct Biol 193, 1– 12 (2016). 26592709 PMC4711343
  34. [38]Zivanov J, New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018). 30412051 PMC6250425
  35. [39]Cook AD, Manka SW, Wang S, Moores CA, Atherton J, A microtubule RELION-based pipeline for cryo-EM image processing. J Struct Biol 209, 107402 (2020). 31610239 PMC6961209
  36. [40]Grigorieff N, Frealign: An Exploratory Tool for Single-Particle Cryo-EM. Methods in Enzymology 579, 191– 226 (2016). 27572728 PMC6760665
  37. [41]Alushin GM, High-resolution microtubule structures reveal the structural transitions in alphabeta-tubulin upon GTP hydrolysis. Cell 157, 1117– 1129 (2014). 24855948 PMC4054694
  38. [42]Zhang R, Nogales E, A new protocol to accurately determine microtubule lattice seam location. J Struct Biol 192, 245– 254 (2015). 26424086 PMC4634897
  39. [43]Grant T, Rohou A, Grigorieff N, cisTEM, user-friendly software for single-particle image processing. eLife 7, e35383 (2018). 29513216 PMC5854467
  40. [44]Debs GE, Cha M, Liu X, Huehn AR, Sindelar CV, Dynamic and asymmetric fluctuations in the microtubule wall captured by high-resolution cryoelectron microscopy. PNAS 117, 16976– 16984 (2020). 32636254 PMC7382274
  41. [45]Emsley P, Cowtan K, Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60, 2126– 2132 (2004). 15572765
  42. [46]DiMaio F, Tyka MD, Baker ML, Chiu W, Baker D, Refinement of protein structures into low-resolution density maps using rosetta. J Mol Biol 392, 181– 190 (2009). 19596339 PMC3899897
  43. [47]Tyka MD, Alternate states of proteins revealed by detailed energy landscape mapping. J Mol Biol 405, 607– 618 (2011). 21073878 PMC3046547
  44. [48]Castoldi M, Popov AV, Purification of brain tubulin through two cycles of polymerization-depolymerization in a high-molarity buffer. Protein Expr Purif 32, 83– 88 (2003). 14680943
  45. [49]Korten T, Chaudhuri S, Tavkin E, Braun M, Diez S, Kinesin-1 Expressed in Insect Cells Improves Microtubule in Vitro Gliding Performance, Long-Term Stability and Guiding Efficiency in Nanostructures. IEEE Trans Nanobioscience 15, 62– 69 (2016). 26886999
  46. [50]Yildiz A, Myosin V walks hand-over-hand: single fluorophore imaging with 1.5-nm localization. Science 300, 2061– 2065 (2003). 12791999
  47. [51]Belyy V, Hendel NL, Chien A, Yildiz A, Cytoplasmic dynein transports cargos via load-sharing between the heads. Nature Comm 5, 5544 (2014). PMC4410804 25424027
  48. [52]Phillips JC, Scalable molecular dynamics on CPU and GPU architectures with NAMD. JCP 153, 044130 (2020). PMC7395834 32752662
  49. [53]Best RB, Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone ϕ, ψ and side-chain χ1 and χ2 dihedral angles. Journal of Chemical Theory and Computation 8, 3257– 3273 (2012). 23341755 PMC3549273
  50. [54]Beckstein O, Denning EJ, Perilla JR, Woolf TB, Zipping and unzipping of adenylate kinase: atomistic insights into the ensemble of open↔ closed transitions. Journal of Molecular Biology 394, 160– 176 (2009). 19751742 PMC2803350
  51. [55]Durrant JD, McCammon JA, HBonanza: a computer algorithm for molecular-dynamics-trajectory hydrogen-bond analysis. Journal of Molecular Graphics and Modelling 31, 5– 9 (2011). 21880522 PMC3218086
  52. [56]Heymann JB, Single particle reconstruction and validation using Bsoft for the map challenge. J Struct Biol 204, 90– 95 (2018). 29981840 PMC6119472
  53. [57]Cole C, Barber JD, Barton GJ, The Jpred 3 secondary structure prediction server. NAR 36, 197– 201 (2008). PMC2447793 18463136

Cited by

Sorted by citations

Authors
Ferro, L. S., Fang, Q., Eshun-Wilson, L., Fernandes, J., Jack, A., Farrell, D. P., Golcuk, M., Huijben, T., Costa, K., Gur, M., DiMaio, F., Nogales, E., & Yildiz, A.
Affiliations
  • University of California, Berkeley (US)
  • University of Washington (US)
  • Department of Mechanical Engineering, Istanbul Technical University, Istanbul, Turkey.
  • Delft University of Technology (NL)
  • Press West Illustrations, Boston, MA, USA.
  • Howard Hughes Medical Institute (US)
  • Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Corresponding author
  • Ferro, Luke S.
  • Fang, Qianglin
  • Eshun-Wilson, Lisa
  • Fernandes, Jonathan
  • Nogales, Eva
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2022-01-21
Volume
375
Issue
6578
Pages
326-331
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.abf6154
PMC
PMC8985661
OpenAlex
W4206569790
Cited by
112
References
4
Citations by year
2026: 25 · 2025: 23 · 2024: 21 · 2023: 29 · 2022: 14
FWCI
11.61
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion, cc-by)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Istanbul Technical University Academic Open Archive (Istanbul Technical University) (submittedVersion)
  • Research Repository (Delft University of Technology) (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • National Science Foundation (GM127018, 1055017, 1617028)
  • Howard Hughes Medical Institute
  • University of California Berkeley
  • Partnership for Advanced Computing in Europe AISBL
  • Istanbul Teknik Üniversitesi
  • National Institute of General Medical Sciences (T32GM008295, P01GM051487, GM 051487, R01GM094522, GM123655-03, GM094522, F31GM123655, R35GM136414, R35GM127018, R01GM123089)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
kinesin-1, MAP7, microtubule-associated proteins, microtubule-binding domain, intracellular cargo transport, competitive binding, projection domain, microtubule protofilaments
MeSH terms
Protein Domains, Protein Conformation, alpha-Helical, Binding Sites, Binding, Competitive, Dyneins, Humans, Microtubule-Associated Proteins, Microtubules, Models, Biological, Models, Molecular, Protein Binding, Tubulin, Kinesins, Cryoelectron Microscopy

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