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

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Abstract

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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Acknowledgements

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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