CoChat
Sign Up
Cited by 54

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport

Celestino, Ricardo, Gama, José B., Castro-Rodrigues, Artur F., Barbosa, Daniel J., Rocha, Helder, d’Amico, Ennio A., Musacchio, Andrea, Carvalho, Ana Xavier, Morais-Cabral, João H., Gassmann, Reto·2022·Journal of Cell Biology
DOI 10.1083/jcb.202110057PMC PMC9284427

Published version of a preprint

Open this paper in CoChat — free account

Abstract

The MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates and invertebrates. How JIP3’s interaction with dynein and kinesin-1 contributes to organelle clearance is unclear. We show that human dynein light intermediate chain (DLIC) binds the N-terminal RH1 domain of JIP3, its paralog JIP4, and the lysosomal adaptor RILP. A point mutation in RH1 abrogates DLIC binding without perturbing the interaction between JIP3’s RH1 domain and kinesin heavy chain. Characterization of this separation-of-function mutation in Caenorhabditis elegans shows that JIP3–bound dynein is required for organelle clearance in the anterior process of touch receptor neurons. Unlike JIP3 null mutants, JIP3 that cannot bind DLIC causes prominent accumulation of endo-lysosomal organelles at the neurite tip, which is rescued by a disease-associated point mutation in JIP3’s leucine zipper that abrogates kinesin light chain binding. These results highlight that RH1 domains are interaction hubs for cytoskeletal motors and suggest that JIP3–bound dynein and kinesin-1 participate in bidirectional organelle transport.

Overview

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 · 10.1083/jcb.202110057

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

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?

  • JIP4 is a large scaffold that binds both dynein and kinesin-1.

    “JIP4 is a large scaffold that binds both dynein and, notably, also kinesin-1, which mediates anterograde organelle transport (Celestino et al., 2022;Montagnac et al., 2009;Nguyen et al., 2005;Verhey et al., 2001;Vilela et al., 2019).”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Celestino et al., 2022

    The Results section (page unavailable) reports that JIP4’s RH1 domain binds the dynein light intermediate chain. The paper’s kinesin-1 binding experiments concern JIP3, not JIP4, so this source does not establish the claimed JIP4–kinesin-1 interaction. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null) worms.

    “However, UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null)worms”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Celestino et al., 2022

    The Results section, “Dynein light intermediate chain binding is essential for UNC-16 function in vivo,” reports that unc-16 loss-of-function animals are locomotion deficient, supporting the uncoordinated-movement part of the claim. Our copy does not report a phenotype for Y71H2AM.2(null) worms, so it does not support the comparison. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The phenotype of Y71H2AM.2(null) worms reflects in many regards that of worms depleted of the JIP3/4 homolog UNC-16, in particular the redistribution of lysosomes to the more proximal axon.

    “The phenotype of the Y71H2AM.2(null)worms interestingly reflects in many regards that of worms depleted of the JIP3/4 homolog UNC-16 (the C. elegans homolog of JIP3/4), in particular the redistribution of lysosomes to the more proximal axon (Celestino et al., 2022;Edwards et al., 2015;Edwards et al., 2013)”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Celestino et al., 2022

Self-check

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

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

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 58

  1. Abe, 2009, Sunday driver interacts with two distinct classes of axonal organelles, J. Biol. Chem., 284, 34628, 10.1074/jbc.M109.035022 · DOI
  2. Arimoto, 2011, The Caenorhabditis elegans JIP3 protein UNC-16 functions as an adaptor to link kinesin-1 with cytoplasmic dynein, J. Neurosci., 31, 2216, 10.1523/JNEUROSCI.2653-10.2011 · DOI
  3. Arribere, 2014, Efficient marker-free recovery of custom genetic modifications with CRISPR/Cas9 in Caenorhabditis elegans, Genetics, 198, 837, 10.1534/genetics.114.169730 · DOI
  4. Becker, 2006, Pin1 mediates neural-specific activation of the mitochondrial apoptotic machinery, Neuron, 49, 655, 10.1016/j.neuron.2006.01.034 · DOI
  5. Bowman, 2000, Kinesin-dependent axonal transport is mediated by the sunday driver (SYD) protein, Cell, 103, 583, 10.1016/s0092-8674(00)00162-8 · DOI
  6. Byrd, 2001, UNC-16, a JNK-signaling scaffold protein, regulates vesicle transport in C. elegans, Neuron, 32, 787, 10.1016/s0896-6273(01)00532-3 · DOI
  7. Cason, 2021, Sequential dynein effectors regulate axonal autophagosome motility in a maturation-dependent pathway, J. Cell Biol., 220, 10.1083/jcb.202010179 · DOI
  8. Cavalli, 2005, Sunday Driver links axonal transport to damage signaling, J. Cell Biol., 168, 775, 10.1083/jcb.200410136 · DOI
  9. Celestino, 2019, A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport, PLoS Biol., 17, 10.1371/journal.pbio.3000100 · DOI
  10. Chaaban, 2022, Structure of dynein-dynactin on microtubules shows tandem recruitment of cargo adaptors, bioRxiv, 10.1101/2022.03.17.482250 · DOI
  11. Choudhary, 2017, UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes, PLoS Genet., 13, 10.1371/journal.pgen.1007100 · DOI
  12. Cockburn, 2018, Insights into kinesin-1 activation from the crystal structure of KLC2 bound to JIP3, Structure, 26, 1486, 10.1016/j.str.2018.07.011 · DOI
  13. Drerup, 2013, JNK-interacting protein 3 mediates the retrograde transport of activated c-Jun N-terminal kinase and lysosomes, PLoS Genet., 9, 10.1371/journal.pgen.1003303 · DOI
  14. Edwards, 2015, UNC-16 (JIP3) acts through synapse-assembly proteins to inhibit the active transport of cell soma organelles to Caenorhabditis elegans motor neuron axons, Genetics, 201, 117, 10.1534/genetics.115.177345 · DOI · Paper page
  15. Edwards, 2013, An organelle gatekeeper function for Caenorhabditis elegans UNC-16 (JIP3) at the axon initial segment, Genetics, 194, 143, 10.1534/genetics.112.147348 · DOI · Paper page
  16. Frøkjaer-Jensen, 2012, Improved Mos1-mediated transgenesis in C. elegans, Nat. Methods, 9, 117, 10.1038/nmeth.1865 · DOI
  17. Gama, 2017, Molecular mechanism of dynein recruitment to kinetochores by the Rod–Zw10–Zwilch complex and Spindly, J. Cell Biol., 216, 943, 10.1083/jcb.201610108 · DOI
  18. Gowrishankar, 2021, Overlapping roles of JIP3 and JIP4 in promoting axonal transport of lysosomes in human iPSC-derived neurons, Mol. Biol. Cell, 32, 1094, 10.1091/mbc.E20-06-0382 · DOI · Paper page
  19. Gowrishankar, 2017, Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology, J. Cell Biol., 216, 3291, 10.1083/jcb.201612148 · DOI · Paper page
  20. Hall, 1991, Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans, Cell, 65, 837, 10.1016/0092-8674(91)90391-b · DOI
  21. Hammond, 2008, Co-operative versus independent transport of different cargoes by kinesin-1, Traffic, 9, 725, 10.1111/j.1600-0854.2008.00722.x · DOI
  22. Hill, 2019, Maturation and clearance of autophagosomes in neurons depends on a specific cysteine protease isoform, ATG-4.2, Dev. Cell, 49, 251, 10.1016/j.devcel.2019.02.013 · DOI
  23. Huang, 2011, JIP3 mediates TrkB axonal anterograde transport and enhances BDNF signaling by directly bridging TrkB with kinesin-1, J. Neurosci., 31, 10602, 10.1523/JNEUROSCI.0436-11.2011 · DOI
  24. Ito, 1999, JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a scaffold factor in the JNK signaling pathway, Mol. Cell. Biol., 19, 7539, 10.1128/MCB.19.11.7539 · DOI · Paper page
  25. Iwasawa, 2019, Recurrent de novo MAPK8IP3 variants cause neurological phenotypes, Ann. Neurol., 85, 927, 10.1002/ana.25481 · DOI
  26. Jordens, 2001, The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors, Curr. Biol., 11, 1680, 10.1016/S0960-9822(01)00531-0 · DOI · Paper page
  27. Lee, 2018, A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity, Nat. Commun., 9, 986, 10.1038/s41467-018-03412-8 · DOI
  28. Lee, 2020, A tunable LIC1-adaptor interaction modulates dynein activity in a cargo-specific manner, Nat. Commun., 11, 5695, 10.1038/s41467-020-19538-7 · DOI
  29. Lisé, 2009, Myosin-Va-interacting protein, RILPL2, controls cell shape and neuronal morphogenesis via Rac signaling, J. Cell Sci., 122, 3810, 10.1242/jcs.050344 · DOI
  30. Ma, 2017, JIP3 regulates neuronal radial migration by mediating TrkB axonal anterograde transport in the developing cerebral cortex, Biochem. Biophys. Res. Commun., 485, 790, 10.1016/j.bbrc.2017.02.132 · DOI
  31. Miller, 2017, Keeping neuronal cargoes on the right track: New Insights into regulators of axonal transport, Neuroscientist, 23, 232, 10.1177/1073858416648307 · DOI
  32. Montagnac, 2009, ARF6 Interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis, Curr. Biol., 19, 184, 10.1016/j.cub.2008.12.043 · DOI · Paper page
  33. Muresan, 2005, c-Jun NH2-terminal kinase-interacting protein-3 facilitates phosphorylation and controls localization of amyloid-beta precursor protein, J. Neurosci., 25, 3741, 10.1523/JNEUROSCI.0152-05.2005 · DOI
  34. Neumann, 2017, KymoAnalyzer: A software tool for the quantitative analysis of intracellular transport in neurons, Traffic, 18, 71, 10.1111/tra.12456 · DOI
  35. Nguyen, 2005, JLP associates with kinesin light chain 1 through a novel leucine zipper-like domain, J. Biol. Chem., 280, 30185, 10.1074/jbc.M505499200 · DOI · Paper page
  36. Paix, 2014, Scalable and versatile genome editing using linear DNAs with microhomology to Cas9 Sites in Caenorhabditis elegans, Genetics, 198, 1347, 10.1534/genetics.114.170423 · DOI
  37. Patel, 1993, Cloning by insertional mutagenesis of a cDNA encoding Caenorhabditis elegans kinesin heavy chain, Proc. Natl. Acad. Sci. USA, 90, 9181, 10.1073/pnas.90.19.9181 · DOI · Paper page
  38. Platzer, 2019, De novo variants in MAPK8IP3 cause intellectual disability with variable brain anomalies, Am. J. Human Genet., 104, 203, 10.1016/j.ajhg.2018.12.008 · DOI
  39. Reck-Peterson, 2018, The cytoplasmic dynein transport machinery and its many cargoes, Nat. Rev. Mol. Cell Biol, 19, 382, 10.1038/s41580-018-0004-3 · DOI
  40. Renna, 2020, Organizational principles of the NuMA-dynein interaction interface and implications for mitotic spindle functions, Structure, 28, 820, 10.1016/j.str.2020.04.017 · DOI
  41. Sakamoto, 2005, The Caenorhabditis elegans UNC-14 RUN domain protein binds to the kinesin-1 and UNC-16 complex and regulates synaptic vesicle localization, Mol. Biol. Cell, 16, 483, 10.1091/mbc.e04-07-0553 · DOI
  42. Sato, 2015, JSAP1/JIP3 and JLP regulate kinesin-1-dependent axonal transport to prevent neuronal degeneration, Cell Death Differ., 22, 1260, 10.1038/cdd.2014.207 · DOI
  43. Schaub, 2013, The Rilp-like proteins Rilpl1 and Rilpl2 regulate ciliary membrane content, Mol. Biol. Cell, 24, 453, 10.1091/mbc.E12-08-0598 · DOI
  44. Schroeder, 2014, A Ras-like domain in the light intermediate chain bridges the dynein motor to a cargo-binding region, eLife, 3, 10.7554/eLife.03351 · DOI
  45. Sun, 2011, Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility, EMBO J., 30, 3416, 10.1038/emboj.2011.229 · DOI
  46. Sun, 2013, c-Jun NH2-terminal kinase (JNK)-interacting protein-3 (JIP3) regulates neuronal axon elongation in a kinesin- and JNK-dependent manner, J. Biol. Chem., 288, 14531, 10.1074/jbc.M113.464453 · DOI
  47. Sun, 2017, JIP1 and JIP3 cooperate to mediate TrkB anterograde axonal transport by activating kinesin-1, Cell Mol. Life Sci., 74, 4027, 10.1007/s00018-017-2568-z · DOI
  48. Sure, 2018, UNC-16/JIP3 and UNC-76/FEZ1 limit the density of mitochondria in C. elegans neurons by maintaining the balance of anterograde and retrograde mitochondrial transport, Sci. Rep., 8, 8938, 10.1038/s41598-018-27211-9 · DOI
  49. Urnavicius, 2018, Cryo-EM shows how dynactin recruits two dyneins for faster movement, Nature, 554, 202, 10.1038/nature25462 · DOI
  50. Urnavicius, 2015, The structure of the dynactin complex and its interaction with dynein, Science, 347, 1441, 10.1126/science.aaa4080 · DOI · Paper page
  51. Verhey, 2001, Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules, J. Cell Biol., 152, 959, 10.1083/jcb.152.5.959 · DOI · Paper page
  52. Vilela, 2019, Structural characterization of the RH1-LZI tandem of JIP3/4 highlights RH1 domains as a cytoskeletal motor-binding motif, Sci. Rep., 9, 10.1038/s41598-019-52537-3 · DOI
  53. Villanueva, 2001, jkk-1 and mek-1 regulate body movement coordination and response to heavy metals through jnk-1 in Caenorhabditis elegans, EMBO J., 20, 5114, 10.1093/emboj/20.18.5114 · DOI
  54. Wang, 2004, A unique region of RILP distinguishes it from its related proteins in its regulation of lysosomal morphology and interaction with Rab7 and Rab34, Mol. Biol. Cell, 15, 815, 10.1091/mbc.E03-06-0413 · DOI
  55. Watt, 2015, JIP3 activates kinesin-1 motility to promote axon elongation, J. Biol. Chem., 290, 15512, 10.1074/jbc.M115.651885 · DOI · Paper page
  56. Wei, 2013, Structural basis of cargo recognitions for class V myosins, Proc. Natl. Acad. Sci. USA, 110, 11314, 10.1073/pnas.1306768110 · DOI
  57. Wu, 2005, Structural basis for recruitment of RILP by small GTPase Rab7, EMBO J., 24, 1491, 10.1038/sj.emboj.7600643 · DOI
  58. Yan, 2013, Kinesin-1 regulates dendrite microtubule polarity in Caenorhabditis elegans, eLife, 2, 10.7554/eLife.00133 · DOI

Cited by

Sorted by citations

Metadata

Authors
Celestino, R., Gama, J. B., Castro-Rodrigues, A. F., Barbosa, D. J., Rocha, H., d’Amico, E. A., Musacchio, A., Carvalho, A. X., Morais-Cabral, J. H., & Gassmann, R.
Affiliations
  • Instituto de Investigação e Inovação em Saúde—i3S, Universidade do Porto, Porto, Portugal 1
  • Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany 3
ORCID
Venue
Journal of Cell Biology
Publisher
Rockefeller University Press
Published
2022-07-13
Volume
221
Issue
8
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.202110057
PMC
PMC9284427
Cited by
54
References
4
Language
en
Licence
Funders
  • Oklahoma Medical Research Foundation
  • Office of Research Infrastructure Programs (P40 OD010440)
  • Fundação para a Ciência e a Tecnologia (PTDC/BIA-CEL/30507/2017, PTDC/BIA-CEL/1321/2021, CEECIND/00333/2017, CEECIND/01967/2017, DL57/2016/CP1355/CT0001, DL57/2016/CP1355/CT0007)

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