Lyons David A, Naylor Stephen G, Scholze Anja, Talbot William S
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA, USA.
Nat Genet. 2009 Jul;41(7):854-8. doi: 10.1038/ng.376. Epub 2009 Jun 7.
The kinesin motor protein Kif1b has previously been implicated in the axonal transport of mitochondria and synaptic vesicles. More recently, KIF1B has been associated with susceptibility to multiple sclerosis (MS). 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.
驱动蛋白Kif1b此前被认为与线粒体和突触小泡的轴突运输有关。最近,KIF1B与多发性硬化症(MS)的易感性相关。在这里,我们表明Kif1b是斑马鱼中髓鞘碱性蛋白(mbp)mRNA定位于髓鞘形成少突胶质细胞突起所必需的。我们在kif1b突变体中观察到类髓鞘膜的异位出现,这与髓鞘蛋白在kif1b突变体少突胶质细胞胞体中的异位定位一致。这些观察结果表明,少突胶质细胞将某些mRNA分子(即那些编码如MBP等小碱性蛋白的分子)定位,以防止这些蛋白在细胞其他部位产生异常影响。我们还发现,Kif1b是外周和中枢神经系统中一些最长轴突生长所必需的。我们的数据证明了kif1b在体内以前未知的功能,并为其在MS中的可能作用提供了见解。