The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.
The kinesin-3 family motor KLP-4 regulates anterograde trafficking of GLR-1 glutamate receptors in the ventral nerve cord of Caenorhabditis elegans.
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DOI：
10.1091/mbc.e12-04-0334
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发表时间：
2012-09
影响因子：
3.3
通讯作者：
Juo P
中科院分区：
文献类型：
--
作者：
Monteiro MI;Ahlawat S;Kowalski JR;Malkin E;Koushika SP;Juo P
细胞周期蛋白依赖性激酶-5和驱动蛋白-3家族马达KLP-4在相同的途径中起作用，以促进秀丽隐杆线虫腹侧神经索中谷氨酸受体的顺行运输。这项研究揭示了一种细胞控制机制，通过这种机制，受体货物在缺乏其马达的情况下被靶向降解。谷氨酸受体从细胞体到突触的转运在神经元发育过程中是必不可少的，并且可能有助于成熟神经系统中突触强度的调节。我们先前表明，细胞周期蛋白依赖性激酶-5（CDK-5）正调控秀丽隐杆线虫腹神经索（VNC）突触处GLR-1谷氨酸受体的丰度。在这里，我们确定了一个驱动蛋白-3家族电机klp-4/KIF 13在cdk-5抑制筛选基因，调节GLR-1贩运。klp-4突变体降低了VNC中GLR-1的丰度。klp-4和网格蛋白适应素unc-11/AP 180的遗传分析表明，klp-4在腹索中的内吞作用之前起作用。延时显微镜显示klp-4突变体表现出GLR-1的顺行通量降低。cdk-5和klp-4的遗传分析表明，它们在VNC中以相同的途径调节GLR-1。有趣的是，GLR-1在cdk-5而不是klp-4突变体的细胞体中积累。然而，如果多泡体/溶酶体途径中的受体降解被阻断，则GLR-1确实在klp-4突变体细胞体中积累。这项研究确定驱动蛋白KLP-4作为一种新的调节剂的顺行谷氨酸受体运输，并揭示了细胞控制机制，受体货物的目标降解在其电机的情况下。
Cyclin-dependent kinase-5 and the kinesin-3 family motor KLP-4 function in the same pathway to promote anterograde trafficking of glutamate receptors in the ventral nerve cord of Caenorhabditis elegans. This study reveals a cellular control mechanism by which receptor cargo is targeted for degradation in the absence of its motor. The transport of glutamate receptors from the cell body to synapses is essential during neuronal development and may contribute to the regulation of synaptic strength in the mature nervous system. We previously showed that cyclin-dependent kinase-5 (CDK-5) positively regulates the abundance of GLR-1 glutamate receptors at synapses in the ventral nerve cord (VNC) of Caenorhabditis elegans. Here we identify a kinesin-3 family motor klp-4/KIF13 in a cdk-5 suppressor screen for genes that regulate GLR-1 trafficking. klp-4 mutants have decreased abundance of GLR-1 in the VNC. Genetic analysis of klp-4 and the clathrin adaptin unc-11/AP180 suggests that klp-4 functions before endocytosis in the ventral cord. Time-lapse microscopy indicates that klp-4 mutants exhibit decreased anterograde flux of GLR-1. Genetic analysis of cdk-5 and klp-4 suggests that they function in the same pathway to regulate GLR-1 in the VNC. Interestingly, GLR-1 accumulates in cell bodies of cdk-5 but not klp-4 mutants. However, GLR-1 does accumulate in klp-4–mutant cell bodies if receptor degradation in the multivesicular body/lysosome pathway is blocked. This study identifies kinesin KLP-4 as a novel regulator of anterograde glutamate receptor trafficking and reveals a cellular control mechanism by which receptor cargo is targeted for degradation in the absence of its motor.