Marszalek J R, Weiner J A, Farlow S J, Chun J, Goldstein L S
Biomedical Sciences Graduate Program, Division of Cellular and Molecular Medicine, Department of Pharmacology, University of California San Diego, La Jolla, California 92093-0683, USA.
J Cell Biol. 1999 May 3;145(3):469-79. doi: 10.1083/jcb.145.3.469.
Neurons use kinesin and dynein microtubule-dependent motor proteins to transport essential cellular components along axonal and dendritic microtubules. In a search for new kinesin-like proteins, we identified two neuronally enriched mouse kinesins that provide insight into a unique intracellular kinesin targeting mechanism in neurons. KIF21A and KIF21B share colinear amino acid similarity to each other, but not to any previously identified kinesins outside of the motor domain. Each protein also contains a domain of seven WD-40 repeats, which may be involved in binding to cargoes. Despite the amino acid sequence similarity between KIF21A and KIF21B, these proteins localize differently to dendrites and axons. KIF21A protein is localized throughout neurons, while KIF21B protein is highly enriched in dendrites. The plus end-directed motor activity of KIF21B and its enrichment in dendrites indicate that models suggesting that minus end-directed motor activity is sufficient for dendrite specific motor localization are inadequate. We suggest that a novel kinesin sorting mechanism is used by neurons to localize KIF21B protein to dendrites since its mRNA is restricted to the cell body.
神经元利用驱动蛋白和动力蛋白这两种依赖微管的运动蛋白，沿着轴突和树突微管运输重要的细胞成分。在寻找新的驱动蛋白样蛋白的过程中，我们鉴定出了两种在神经元中高度富集的小鼠驱动蛋白，它们为神经元中一种独特的细胞内驱动蛋白靶向机制提供了深入见解。KIF21A和KIF21B彼此具有共线性氨基酸相似性，但与运动结构域之外的任何先前鉴定的驱动蛋白都没有相似性。每种蛋白还包含一个由七个WD-40重复序列组成的结构域，该结构域可能参与与货物的结合。尽管KIF21A和KIF21B之间存在氨基酸序列相似性，但这些蛋白在树突和轴突中的定位有所不同。KIF21A蛋白遍布神经元，而KIF21B蛋白在树突中高度富集。KIF21B的正向运动活性及其在树突中的富集表明，那些认为负向运动活性足以实现树突特异性运动蛋白定位的模型是不充分的。我们认为，神经元利用一种新的驱动蛋白分选机制将KIF21B蛋白定位到树突，因为其mRNA局限于细胞体。
