Sato Tokiharu, Ishikawa Momoe, Yoshihara Toru, Nakazato Ryota, Higashida Haruhiro, Asano Masahide, Yoshioka Katsuji
Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Division of Transgenic Animal Science, Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640, Japan.
FEBS Lett. 2015 Sep 14;589(19 Pt B):2805-11. doi: 10.1016/j.febslet.2015.08.024. Epub 2015 Aug 29.
JNK/stress-activated protein kinase-associated protein 1 (JSAP1) and JNK-associated leucine zipper protein (JLP) are structurally related scaffolding proteins that are highly expressed in the brain. Here, we found that JSAP1 and JLP play functionally redundant and essential roles in mouse cerebellar Purkinje cell (PC) survival. Mice containing PCs with deletions in both JSAP1 and JLP exhibited PC axonal dystrophy, followed by gradual, progressive neuronal loss. Kinesin-1 cargoes accumulated selectively in the swollen axons of Jsap1/Jlp-deficient PCs. In addition, autophagy inactivation in these mice markedly accelerated PC degeneration. These findings suggest that JSAP1 and JLP play critical roles in kinesin-1-dependent axonal transport, which prevents brain neuronal degeneration.
JNK/应激激活蛋白激酶相关蛋白1（JSAP1）和JNK相关亮氨酸拉链蛋白（JLP）是结构相关的支架蛋白，在大脑中高度表达。在此，我们发现JSAP1和JLP在小鼠小脑浦肯野细胞（PC）存活中发挥功能冗余且必不可少的作用。在JSAP1和JLP均缺失的PC小鼠中，出现了PC轴突营养不良，随后是逐渐的、进行性的神经元丧失。驱动蛋白-1货物选择性地积聚在Jsap1/Jlp缺陷型PC的肿胀轴突中。此外，这些小鼠的自噬失活显著加速了PC变性。这些发现表明，JSAP1和JLP在驱动蛋白-1依赖性轴突运输中起关键作用，从而防止脑神经元变性。
