CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon
Autoři:
Ying-Chun Chen aff001; Hao-Ru Huang aff001; Chia-Hao Hsu aff001; Chan-Yen Ou aff001
Působiště autorů:
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
aff001
Vyšlo v časopise:
CRMP/UNC-33 organizes microtubule bundles for KIF5-mediated mitochondrial distribution to axon. PLoS Genet 17(2): e1009360. doi:10.1371/journal.pgen.1009360
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009360
Souhrn
Neurons are highly specialized cells with polarized cellular processes and subcellular domains. As vital organelles for neuronal functions, mitochondria are distributed by microtubule-based transport systems. Although the essential components of mitochondrial transport including motors and cargo adaptors are identified, it is less clear how mitochondrial distribution among somato-dendritic and axonal compartment is regulated. Here, we systematically study mitochondrial motors, including four kinesins, KIF5, KIF17, KIF1, KLP-6, and dynein, and transport regulators in C. elegans PVD neurons. Among all these motors, we found that mitochondrial export from soma to neurites is mainly mediated by KIF5/UNC-116. Interestingly, UNC-116 is especially important for axonal mitochondria, while dynein removes mitochondria from all plus-end dendrites and the axon. We surprisingly found one mitochondrial transport regulator for minus-end dendritic compartment, TRAK-1, and two mitochondrial transport regulators for axonal compartment, CRMP/UNC-33 and JIP3/UNC-16. While JIP3/UNC-16 suppresses axonal mitochondria, CRMP/UNC-33 is critical for axonal mitochondria; nearly no axonal mitochondria present in unc-33 mutants. We showed that UNC-33 is essential for organizing the population of UNC-116-associated microtubule bundles, which are tracks for mitochondrial trafficking. Disarrangement of these tracks impedes mitochondrial transport to the axon. In summary, we identified a compartment-specific transport regulation of mitochondria by UNC-33 through organizing microtubule tracks for different kinesin motors other than microtubule polarity.
Klíčová slova:
Mitochondria – Axonal transport – Axons – Microtubules – Motor neurons – Neurites – Neuronal dendrites – Neurons
Zdroje
1. Schwarz TL. Mitochondrial Trafficking in Neurons. Cold Spring Harb Perspect Biol. 2013;5(6):a011304. doi: 10.1101/cshperspect.a011304 23732472
2. Han SM, Baig HS, Hammarlund M. Mitochondria Localize to Injured Axons to Support Regeneration. Neuron. 2016;92(6):1308–23. doi: 10.1016/j.neuron.2016.11.025 28009276
3. Li Z, Okamoto KI, Hayashi Y, Sheng M. The Importance of Dendritic Mitochondria in the Morphogenesis and Plasticity of Spines and Synapses. Cell. 2004;119(6):873–87. doi: 10.1016/j.cell.2004.11.003 15607982
4. Morris RL, Hollenbeck PJ. The regulation of bidirectional mitochondrial transport is coordinated with axonal outgrowth. J Cell Sci. 1993;104:917–27. 8314882
5. Rawson RL, Yam L, Weimer RM, Bend EG, Hartwieg E, Horvitz HR, et al. Axons Degenerate in the Absence of Mitochondria in C. elegans. Curr Biol. 2014;24(7):760–5. doi: 10.1016/j.cub.2014.02.025 24631238
6. Chang DTW, Rintoul GL, Pandipati S, Reynolds IJ. Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis. 2006;22(2):388–400. doi: 10.1016/j.nbd.2005.12.007 16473015
7. Sheng ZH, Cai Q. Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration. Nat Rev Neurosci. 2012;13(2):77–93. doi: 10.1038/nrn3156 22218207
8. Lin MY, Sheng ZH. Regulation of mitochondrial transport in neurons. Exp Cell Res. 2015;334(1):35–44. doi: 10.1016/j.yexcr.2015.01.004 25612908
9. Baas PW, Lin S. Hooks and comets: The story of microtubule polarity orientation in the neuron. Dev Neurobiol. 2011;71(6):403–18. doi: 10.1002/dneu.20818 21557497
10. Guo X, Macleod GT, Wellington A, Hu F, Panchumarthi S, Schoenfield M, et al. The GTPase dMiro is required for axonal transport of mitochondria to Drosophila synapses. Neuron. 2005;47(3):379–93. doi: 10.1016/j.neuron.2005.06.027 16055062
11. Hurd DD, Saxton WM. Kinesin mutations cause motor neuron disease phenotypes by disrupting fast axonal transport in Drosophila. Genetics. 1996;144:1075–85. 8913751
12. Pilling AD, Horiuchi D, Lively CM, Saxton WM. Kinesin-1 and Dynein Are the Primary Motors for Fast Transport of Mitochondria in Drosophila Motor Axons. Mol Biol Cell. 2006;17:2057–68. doi: 10.1091/mbc.e05-06-0526 16467387
13. Stowers RS, Megeath LJ, Górska-Andrzejak J, Meinertzhagen IA, Schwarz TL. Axonal Transport of Mitochondria to Synapses Depends on Milton, a Novel Drosophila Protein. Neuron. 2002;36(6):1063–77. doi: 10.1016/s0896-6273(02)01094-2 12495622
14. Tanaka Y, Kanai Y, Okada Y, Nonaka S, Takeda S, Harada A, et al. Targeted Disruption of Mouse Conventional Kinesin Heavy Chain kif5B, Results in Abnormal Perinuclear Clustering of Mitochondria. Cell. 1998;93(7):1147–58. doi: 10.1016/s0092-8674(00)81459-2 9657148
15. Arimoto M, Koushika SP, Choudhary BC, Li C, Matsumoto K, Hisamoto N. The Caenorhabditis elegans JIP3 Protein UNC-16 Functions As an Adaptor to Link Kinesin-1 with Cytoplasmic Dynein. J Neurosci. 2011;31(6):2216–24. doi: 10.1523/JNEUROSCI.2653-10.2011 21307258
16. Bowman AB, Kamal A, Ritchings BW, Philp AV, McGrail M, Gindhart JG, et al. Kinesin-Dependent Axonal Transport Is Mediated by the Sunday Driver (SYD) Protein. Cell. 2000;103(4):583–94. doi: 10.1016/s0092-8674(00)00162-8 11106729
17. Sun F, Zhu C, Dixit R, Cavalli V. Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility. EMBO J. 2011;30(16):3416–29. doi: 10.1038/emboj.2011.229 21750526
18. Fukata Y, Itoh TJ, Kimura T, Ménager C, Nishimura T, Shiromizu T, et al. CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nat Cell Biol. 2002;4(8):583–91. doi: 10.1038/ncb825 12134159
19. Inagaki N, Chihara K, Arimura N, Ménager C, Kawano Y, Matsuo N, et al. CRMP-2 induces axons in cultured hippocampal neurons. Nat Neurosci. 2001;4(8):781–2. doi: 10.1038/90476 11477421
20. Lin PC, Chan PM, Hall C, Manser E. Collapsin Response Mediator Proteins (CRMPs) Are a New Class of Microtubule-associated Protein (MAP) That Selectively Interacts with Assembled Microtubules via a Taxol-sensitive Binding Interaction. J Biol Chem. 2011;286(48):41466–78. doi: 10.1074/jbc.M111.283580 21953449
21. Niwa S, Nakamura F, Tomabechi Y, Aoki M, Shigematsu H, Matsumoto T, et al. Structural basis for CRMP2-induced axonal microtubule formation. Sci Rep. 2017;7(1):10681. doi: 10.1038/s41598-017-11031-4 28878401
22. Arimura N, Hattori A, Kimura T, Nakamuta S, Funahashi Y, Hirotsune S, et al. CRMP-2 directly binds to cytoplasmic dynein and interferes with its activity. J Neurochem. 2009;111(2):380–90. doi: 10.1111/j.1471-4159.2009.06317.x 19659462
23. Gumy LF, Katrukha EA, Grigoriev I, Jaarsma D, Kapitein LC, Akhmanova A, et al. MAP2 defines a pre-axonal filtering zone to regulate KIF1- versus KIF5-dependent cargo transport in sensory neurons. Neuron. 2017;94(2):347–62. doi: 10.1016/j.neuron.2017.03.046 28426968
24. Karasmanis EP, Phan CT, Angelis D, Kesisova IA, Hoogenraad CC, McKenney RJ, et al. Polarity of Neuronal Membrane Traffic Requires Sorting of Kinesin Motor Cargo during Entry into Dendrites by a Microtubule-Associated Septin. Dev Cell. 2018;46(2):204–218. doi: 10.1016/j.devcel.2018.06.013 30016622
25. Tas RP, Chazeau A, Cloin BMC, Lambers MLA, Hoogenraad CC, Kapitein LC. Differentiation between Oppositely Oriented Microtubules Controls Polarized Neuronal Transport. Neuron. 2017;96(6):1264–1271. doi: 10.1016/j.neuron.2017.11.018 29198755
26. Harterink M, Edwards SL, de Haan B, Yau KW, van den Heuvel S, Kapitein LC, et al. Local microtubule organization promotes cargo transport in C. elegans dendrites. J Cell Sci. 2018;131(20):jcs223107. doi: 10.1242/jcs.223107 30254025
27. Taylor CA, Yan J, Howell AS, Dong X, Shen K. RAB-10 Regulates Dendritic Branching by Balancing Dendritic Transport. PLOS Genet. 2015;11(12):e1005695. doi: 10.1371/journal.pgen.1005695 26633194
28. Karle KN, Möckel D, Reid E, Schöls L. Axonal transport deficit in a KIF5A–/–mouse model. Neurogenetics. 2012;13(2):169–79. doi: 10.1007/s10048-012-0324-y 22466687
29. Nangaku M, Sato-Yoshitake R, Yamazaki H, Hirokawa N. KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell. 1994;79:1209–20. doi: 10.1016/0092-8674(94)90012-4 7528108
30. Tanaka K, Sugiura Y, Ichishita R, Mihara K, Oka T. KLP6: a newly identified kinesin that regulates the morphology and transport of mitochondria in neuronal cells. J Cell Sci. 2011;124(14):2457–65. doi: 10.1242/jcs.086470 21693574
31. Yan J, Chao DL, Toba S, Koyasako K, Yasunaga T, Hirotsune S, et al. Kinesin-1 regulates dendrite microtubule polarity in Caenorhabditis elegans. eLife. 2013;2:e00133. doi: 10.7554/eLife.00133 23482306
32. van Spronsen M, Mikhaylova M, Lipka J, Schlager MA, van den Heuvel DJ, Kuijpers M, et al. TRAK/Milton Motor-Adaptor Proteins Steer Mitochondrial Trafficking to Axons and Dendrites. Neuron. 2013;77(3):485–502. doi: 10.1016/j.neuron.2012.11.027 23395375
33. Li W, Herman RK, Shaw J. Analysis of the Caenorhabditis elegans Axonal Guidance and Outgrowth Gene unc-33. Genetics. 1992;132:675–89. 1468626
34. Kimura T, Arimura N, Fukata Y, Watanabe H, Iwamatsu A, Kaibuchi K. Tubulin and CRMP-2 complex is transported via Kinesin-1. J Neurochem. 2005;93(6):1371–82. doi: 10.1111/j.1471-4159.2005.03063.x 15935053
35. Leterrier C, Dargent B. No Pasaran! Role of the axon initial segment in the regulation of protein transport and the maintenance of axonal identity. Semin Cell Dev Biol. 2014;27:44–51. doi: 10.1016/j.semcdb.2013.11.001 24239676
36. He L, Kooistra R, Das R, Oudejans E, van Leen E, Ziegler J, et al. Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity. eLife. 2020;9:e55111. doi: 10.7554/eLife.55111 32293562
37. Maniar TA, Kaplan M, Wang GJ, Shen K, Wei L, Shaw JE, et al. UNC-33 (CRMP) and ankyrin organize microtubules and localize kinesin to polarize axon-dendrite sorting. Nat Neurosci. 2012;15(1):48–56.
38. Norris AD, Sundararajan L, Morgan DE, Roberts ZJ, Lundquist EA. The UNC-6/Netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone filopodial protrusion via UNC-73/Trio, Rac-like GTPases and UNC-33/CRMP. Development. 2014;141(22):4395–4405. doi: 10.1242/dev.110437 25371370
39. Kawano Y, Yoshimura T, Tsuboi D, Kawabata S, Kaneko-Kawano T, Shirataki H, et al. CRMP-2 Is Involved in Kinesin-1-Dependent Transport of the Sra-1/WAVE1 Complex and Axon Formation. Mol Cell Biol. 2005;25(22):9920–35. doi: 10.1128/MCB.25.22.9920-9935.2005 16260607
40. Deo RC, Schmidt EF, Elhabazi A, Togashi H, Burley SK, Strittmatter SM. Structural bases for CRMP function in plexin-dependent semaphorin3A signaling. EMBO J. 2004;23(1):9–22. doi: 10.1038/sj.emboj.7600021 14685275
41. Wang LH, Strittmatter SM. Brain CRMP Forms Heterotetramers Similar to Liver Dihydropyrimidinase. J Neurochem. 2002;69(6):2261–9.
42. Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, et al. Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation. Nat Commun. 2018;9(1):476. doi: 10.1038/s41467-017-02811-7 29396402
43. Vagnoni A, Bullock SL. A cAMP/PKA/Kinesin-1 Axis Promotes the Axonal Transport of Mitochondria in Aging Drosophila Neurons. Curr Biol. 2018;28(8):1265–1272. doi: 10.1016/j.cub.2018.02.048 29606421
44. Wang X, Schwarz TL. The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial Motility. Cell. 2009;136(1):163–74. doi: 10.1016/j.cell.2008.11.046 19135897
45. Nguyen TT, Oh SS, Weaver D, Lewandowska A, Maxfield D, Schuler MH, et al. Loss of Miro1-directed mitochondrial movement results in a novel murine model for neuron disease. Proc Natl Acad Sci. 2014;111(35):E3631–40. doi: 10.1073/pnas.1402449111 25136135
46. Zinsmaier KE, Babic M, Russo GJ. Mitochondrial Transport Dynamics in Axons and Dendrites. Koenig E Editor. Cell Biol Axon. 2009;48:107–39. doi: 10.1007/400_2009_20 19582407
47. Devine MJ, Birsa N, Kittler JT. Miro sculpts mitochondrial dynamics in neuronal health and disease. Neurobiol Dis. 2016;90:27–34. doi: 10.1016/j.nbd.2015.12.008 26707701
48. Edwards SL, Yu S, Hoover CM, Phillips BC, Richmond JE, Miller KG. An Organelle Gatekeeper Function for Caenorhabditis elegans UNC-16 (JIP3) at the Axon Initial Segment. Genetics. 2013;194(1):143–61. doi: 10.1534/genetics.112.147348 23633144
49. Sure GR, Chatterjee A, Mishra N, Sabharwal V, Devireddy S, Awasthi A, et al. 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. 2018;8(1):8938. doi: 10.1038/s41598-018-27211-9 29895958
50. Tang LT, Diaz-Balzac CA, Rahman M, Ramirez-Suarez NJ, Salzberg Y, Lázaro-Peña MI, et al. TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization. eLife. 2019;8:e38949. doi: 10.7554/eLife.38949 30694177
51. Richardson CE, Yee C, Shen K. A hormone receptor pathway cell-autonomously delays neuron morphological aging by suppressing endocytosis. PLOS Biol. 2019;17(10):e3000452. doi: 10.1371/journal.pbio.3000452 31589601
52. Suzuki H, Kerr R, Bianchi L, Frøkjær-Jensen C, Slone D, Xue J, et al. In Vivo Imaging of C. elegans Mechanosensory Neurons Demonstrates a Specific Role for the MEC-4 Channel in the Process of Gentle Touch Sensation. Neuron. 2003;39(6):1005–17. doi: 10.1016/j.neuron.2003.08.015 12971899
53. Kanaji S, Iwahashi J, Kida Y, Sakaguchi M, Mihara K. Characterization of the Signal That Directs Tom20 to the Mitochondrial Outer Membrane. J Cell Biol. 2000;151(2):277–88. doi: 10.1083/jcb.151.2.277 11038175
54. Kameda H, Furuta T, Matsuda W, Ohira K, Nakamura K, Hioki H, et al. Targeting green fluorescent protein to dendritic membrane in central neurons. Neurosci Res. 2008;61(1):79–91. doi: 10.1016/j.neures.2008.01.014 18342383
55. Evans T. C., ed. Transformation and microinjection (April 6, 2006), WormBook, ed. The C. elegans Research Community, WormBook, doi: 10.1895/wormbook.1.108.1, http://www.wormbook.org.
56. Carvelli L, McDonald PW, Blakely RD, DeFelice LJ. Dopamine transporters depolarize neurons by a channel mechanism. Proc Natl Acad Sci. 2004;101(45):16046–51. doi: 10.1073/pnas.0403299101 15520385
57. Nakata T, Hirokawa N. Point mutation of adenosine triphosphate-binding motif generated rigor kinesin that selectively blocks anterograde lysosome membrane transport. J Cell Biol. 1995;131(4):1039–53. doi: 10.1083/jcb.131.4.1039 7490281
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