6b9h Citations

A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity.

Abstract

Cytoplasmic dynein is the major minus-end-directed microtubule-based motor in cells. Dynein processivity and cargo selectivity depend on cargo-specific effectors that, while generally unrelated, share the ability to interact with dynein and dynactin to form processive dynein-dynactin-effector complexes. How this is achieved is poorly understood. Here, we identify a conserved region of the dynein Light Intermediate Chain 1 (LIC1) that mediates interactions with unrelated dynein-dynactin effectors. Quantitative binding studies map these interactions to a conserved helix within LIC1 and to N-terminal fragments of Hook1, Hook3, BICD2, and Spindly. A structure of the LIC1 helix bound to the N-terminal Hook domain reveals a conformational change that creates a hydrophobic cleft for binding of the LIC1 helix. The LIC1 helix competitively inhibits processive dynein-dynactin-effector motility in vitro, whereas structure-inspired mutations in this helix impair lysosomal positioning in cells. The results reveal a conserved mechanism of effector interaction with dynein-dynactin necessary for processive motility.

Articles - 6b9h mentioned but not cited (2)

  1. A conserved interaction of the dynein light intermediate chain with dynein-dynactin effectors necessary for processivity. Lee IG, Olenick MA, Boczkowska M, Franzini-Armstrong C, Holzbaur ELF, Dominguez R. Nat Commun 9 986 (2018)
  2. Dynein activator Hook1 is required for trafficking of BDNF-signaling endosomes in neurons. Olenick MA, Dominguez R, Holzbaur ELF. J Cell Biol 218 220-233 (2019)


Reviews citing this publication (11)

  1. The cytoplasmic dynein transport machinery and its many cargoes. Reck-Peterson SL, Redwine WB, Vale RD, Carter AP. Nat Rev Mol Cell Biol 19 382-398 (2018)
  2. Dynein activators and adaptors at a glance. Olenick MA, Holzbaur ELF. J Cell Sci 132 jcs227132 (2019)
  3. Activation and Regulation of Cytoplasmic Dynein. Canty JT, Yildiz A. Trends Biochem Sci 45 440-453 (2020)
  4. Emerging mechanisms of dynein transport in the cytoplasm versus the cilium. Roberts AJ. Biochem Soc Trans 46 967-982 (2018)
  5. Selective motor activation in organelle transport along axons. Cason SE, Holzbaur ELF. Nat Rev Mol Cell Biol 23 699-714 (2022)
  6. The crosstalk between microtubules, actin and membranes shapes cell division. Rizzelli F, Malabarba MG, Sigismund S, Mapelli M. Open Biol 10 190314 (2020)
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  8. Cargo-Mediated Activation of Cytoplasmic Dynein in vivo. Xiang X, Qiu R. Front Cell Dev Biol 8 598952 (2020)
  9. The Generation of Dynein Networks by Multi-Layered Regulation and Their Implication in Cell Division. Torisawa T, Kimura A. Front Cell Dev Biol 8 22 (2020)
  10. Review: Cytoplasmic dynein motors in photoreceptors. Dahl TM, Baehr W. Mol Vis 27 506-517 (2021)
  11. Disruption of axonal transport in neurodegeneration. Berth SH, Lloyd TE. J Clin Invest 133 e168554 (2023)

Articles citing this publication (38)

  1. Mitochondrial adaptor TRAK2 activates and functionally links opposing kinesin and dynein motors. Fenton AR, Jongens TA, Holzbaur ELF. Nat Commun 12 4578 (2021)
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  12. RUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin. Keren-Kaplan T, Sarić A, Ghosh S, Williamson CD, Jia R, Li Y, Bonifacino JS. Nat Commun 13 1506 (2022)
  13. The FTS-Hook-FHIP (FHF) complex interacts with AP-4 to mediate perinuclear distribution of AP-4 and its cargo ATG9A. Mattera R, Williamson CD, Ren X, Bonifacino JS. Mol Biol Cell 31 963-979 (2020)
  14. Cryo-EM reveals the complex architecture of dynactin's shoulder region and pointed end. Lau CK, O'Reilly FJ, Santhanam B, Lacey SE, Rappsilber J, Carter AP. EMBO J 40 e106164 (2021)
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  17. Dynein Is Required for Rab7-Dependent Endosome Maturation, Retrograde Dendritic Transport, and Degradation. Yap CC, Digilio L, McMahon LP, Wang T, Winckler B. J Neurosci 42 4415-4434 (2022)
  18. Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions. Kumari A, Kumar C, Pergu R, Kumar M, Mahale SP, Wasnik N, Mylavarapu SVS. J Cell Biol 220 e202005184 (2021)
  19. The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor. Agrawal R, Gillies JP, Zang JL, Zhang J, Garrott SR, Shibuya H, Nandakumar J, DeSantis ME. Elife 11 e78201 (2022)
  20. Coil-to-α-helix transition at the Nup358-BicD2 interface activates BicD2 for dynein recruitment. Gibson JM, Cui H, Ali MY, Zhao X, Debler EW, Zhao J, Trybus KM, Solmaz SR, Wang C. Elife 11 e74714 (2022)
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  25. Conformational transitions of the Spindly adaptor underlie its interaction with Dynein and Dynactin. d'Amico EA, Ud Din Ahmad M, Cmentowski V, Girbig M, Müller F, Wohlgemuth S, Brockmeyer A, Maffini S, Janning P, Vetter IR, Carter AP, Perrakis A, Musacchio A. J Cell Biol 221 e202206131 (2022)
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  28. Dync1li1 is required for the survival of mammalian cochlear hair cells by regulating the transportation of autophagosomes. Zhang Y, Zhang S, Zhou H, Ma X, Wu L, Tian M, Li S, Qian X, Gao X, Chai R. PLoS Genet 18 e1010232 (2022)
  29. RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes. Rawat S, Chatterjee D, Marwaha R, Charak G, Kumar G, Shaw S, Khatter D, Sharma S, de Heus C, Liv N, Klumperman J, Tuli A, Sharma M. J Cell Biol 222 e202108001 (2023)
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  31. Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulates microneme exocytosis in Toxoplasma. Chan AW, Broncel M, Yifrach E, Haseley NR, Chakladar S, Andree E, Herneisen AL, Shortt E, Treeck M, Lourido S. Elife 12 RP85654 (2023)
  32. HEATR5B associates with dynein-dynactin and promotes motility of AP1-bound endosomal membranes. Madan V, Albacete-Albacete L, Jin L, Scaturro P, Watson JL, Muschalik N, Begum F, Boulanger J, Bauer K, Kiebler MA, Derivery E, Bullock SL. EMBO J 42 e114473 (2023)
  33. The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein. Garner KEL, Salter A, Lau CK, Gurusaran M, Villemant CM, Granger EP, McNee G, Woodman PG, Davies OR, Burke BE, Allan VJ. J Cell Biol 222 e202204042 (2023)
  34. BICD2 phosphorylation regulates dynein function and centrosome separation in G2 and M. Gallisà-Suñé N, Sànchez-Fernàndez-de-Landa P, Zimmermann F, Serna M, Regué L, Paz J, Llorca O, Lüders J, Roig J. Nat Commun 14 2434 (2023)
  35. Distinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity. He S, Gillies JP, Zang JL, Córdoba-Beldad CM, Yamamoto I, Fujiwara Y, Grantham J, DeSantis ME, Shibuya H. Nat Commun 14 1715 (2023)
  36. Interaction between the mitochondrial adaptor MIRO and the motor adaptor TRAK. Baltrusaitis EE, Ravitch EE, Fenton AR, Perez TA, Holzbaur ELF, Dominguez R. J Biol Chem 299 105441 (2023)
  37. Recombinant dynein light intermediate chain of Haemonchus contortus affects the functions of goat immune cells in vitro. Aimulajiang K, Wen Z, Khand FM, Leghari A, Xu L, Song X, Li X, Yan R. Parasitol Res 121 1699-1707 (2022)
  38. Solution NMR Backbone Assignment of the C-Terminal Region of Human Dynein Light Intermediate Chain 2 (LIC2-C) Unveils Structural Resemblance with Its Homologue LIC1-C. Henen MA, Paukovich N, Prekeris R, Vögeli B. Magnetochemistry 9 166 (2023)