Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons

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The kinesin motor protein Kif1b has previously been implicated in the axonal transport of mitochondria and synaptic vesicles1,2. More recently, KIF1B has been associated with susceptibility to multiple sclerosis (MS)3. Here we show that Kif1b is required for the localization of mbp (myelin basic protein) mRNA to processes of myelinating oligodendrocytes in zebrafish. We observe the ectopic appearance of myelin-like membrane in kif1b mutants, coincident with the ectopic localization of myelin proteins in kif1b mutant oligodendrocyte cell bodies. These observations suggest that oligodendrocytes localize certain mRNA molecules, namely those encoding small basic proteins such as MBP, to prevent aberrant effects of these proteins elsewhere in the cell. We also find that Kif1b is required for outgrowth of some of the longest axons in the peripheral and central nervous systems. Our data demonstrate previously unknown functions of kif1b in vivo and provide insights into its possible roles in MS.

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Figure 1: kif1b is essential for mbp mRNA localization in the CNS.
Figure 2: Kif1b is required for normal axonal outgrowth in the PNS.
Figure 3: Kif1b is required for normal axonal outgrowth in the CNS.
Figure 4: Kif1b functions in oligodendrocytes to localize myelin mRNA and protein.
Figure 5: Abnormalities in myelinated axons in kif1bst43 mutants.
Figure 6: Ectopic myelin-like membrane in kif1bst43 mutants.

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  1. 1

    Nangaku, M. et al. KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria. Cell 79, 1209–1220 (1994).

  2. 2

    Zhao, C. et al. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105, 587–597 (2001).

  3. 3

    Aulchenko, Y.S. et al. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nat. Genet. 40, 1402–1403 (2008).

  4. 4

    Sherman, D.L. & Brophy, P.J. Mechanisms of axon ensheathment and myelin growth. Nat. Rev. Neurosci. 6, 683–690 (2005).

  5. 5

    Brosamle, C. & Halpern, M.E. Characterization of myelination in the developing zebrafish. Glia 39, 47–57 (2002).

  6. 6

    Colman, D.R., Kreibich, G., Frey, A.B. & Sabatini, D.D. Synthesis and incorporation of myelin polypeptides into CNS myelin. J. Cell Biol. 95, 598–608 (1982).

  7. 7

    Carson, J.H., Worboys, K., Ainger, K. & Barbarese, E. Translocation of myelin basic protein mRNA in oligodendrocytes requires microtubules and kinesin. Cell Motil. Cytoskeleton 38, 318–328 (1997).

  8. 8

    Song, J., Carson, J.H., Barbarese, E., Li, F.Y. & Duncan, I.D. RNA transport in oligodendrocytes from the taiep mutant rat. Mol. Cell. Neurosci. 24, 926–938 (2003).

  9. 9

    Ainger, K. et al. Transport and localization of exogenous myelin basic protein mRNA microinjected into oligodendrocytes. J. Cell Biol. 123, 431–441 (1993).

  10. 10

    Pogoda, H.M. et al. A genetic screen identifies genes essential for development of myelinated axons in zebrafish. Dev. Biol. 298, 118–131 (2006).

  11. 11

    Kikkawa, M. et al. Switch-based mechanism of kinesin motors. Nature 411, 439–445 (2001).

  12. 12

    Marchler-Bauer, A. et al. CDD: a conserved domain database for interactive domain family analysis. Nucleic Acids Res. 35, D237–D240 (2007).

  13. 13

    Hirokawa, N. & Takemura, R. Molecular motors and mechanisms of directional transport in neurons. Nat. Rev. Neurosci. 6, 201–214 (2005).

  14. 14

    Sato, T., Takahoko, M. & Okamoto, H. HuC:Kaede, a useful tool to label neural morphologies in networks in vivo. Genesis 44, 136–142 (2006).

  15. 15

    Lyons, D.A., Naylor, S.G., Mercurio, S., Dominguez, C. & Talbot, W.S. KBP is essential for axonal structure, outgrowth and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome. Development 135, 599–608 (2008).

  16. 16

    Schlisio, S. et al. The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev. 22, 884–893 (2008).

  17. 17

    Yeh, I.T. et al. A germline mutation of the KIF1B beta gene on 1p36 in a family with neural and nonneural tumors. Hum. Genet. 124, 279–285 (2008).

  18. 18

    Munirajan, A.K. et al. KIF1Bbeta functions as a haploinsufficient tumor suppressor gene mapped to chromosome 1p36.2 by inducing apoptotic cell death. J. Biol. Chem. 283, 24426–24434 (2008).

  19. 19

    Cahoy, J.D. et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J. Neurosci. 28, 264–278 (2008).

  20. 20

    Shin, J., Park, H.C., Topczewska, J.M., Mawdsley, D.J. & Appel, B. Neural cell fate analysis in zebrafish using olig2 BAC transgenics. Methods Cell Sci. 25, 7–14 (2003).

  21. 21

    Lyons, D.A. et al. erbb3 and erbb2 are essential for schwann cell migration and myelination in zebrafish. Curr. Biol. 15, 513–524 (2005).

  22. 22

    Morris, J.K. et al. The 36K protein of zebrafish CNS myelin is a short-chain dehydrogenase. Glia 45, 378–391 (2004).

  23. 23

    Gould, R.M., Freund, C.M. & Barbarese, E. Myelin-associated oligodendrocytic basic protein mRNAs reside at different subcellular locations. J. Neurochem. 73, 1913–1924 (1999).

  24. 24

    Rispoli, P. et al. A thermodynamic and structural study of myelin basic protein in lipid membrane models. Biophys. J. 93, 1999–2010 (2007).

  25. 25

    Hauser, S.L. & Oksenberg, J.R. The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 52, 61–76 (2006).

  26. 26

    Meinl, E. & Hohlfeld, R. Immunopathogenesis of multiple sclerosis: MBP and beyond. Clin. Exp. Immunol. 128, 395–397 (2002).

  27. 27

    Hedegaard, C.J. et al. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology 125, 161–169 (2008).

  28. 28

    Lambracht-Washington, D. et al. Antigen specificity of clonally expanded and receptor edited cerebrospinal fluid B cells from patients with relapsing remitting MS. J. Neuroimmunol. 186, 164–176 (2007).

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We thank I. Middendorf, T. Reyes and C. Hill for technical support and fish care. We thank H. Okamoto, B. Appel, G. Jeserich and M. Meyer for sharing reagents. We thank B. Barres, P. Brophy and members of our laboratory for comments on the manuscript. This work was supported by grants from the US National Institutes of Health (NS050223, W.S.T.) and the National Multiple Sclerosis Society (RG 3943-A-2, W.S.T.), a postdoctoral fellowship from the Muscular Dystrophy Association (MDA4061, D.A.L.) and a David Phillips Fellowship from the Biotechnology and Biological Sciences Research Council, UK (D.A.L.).

Author information

W.S.T. and D.A.L. designed the study. D.A.L. performed the phenotypic assessment of mutant, morphant and chimeric zebrafish, with contributions from A.S. S.G.N. mapped the st43 mutation to kif1b. D.A.L. and W.S.T. wrote this paper.

Correspondence to William S Talbot.

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