Neuronal polarity is regulated by a direct interaction between a scaffolding protein, Neurabin, and a presynaptic SAD-1 kinase in Caenorhabditis elegans

被引:57
作者
Hung, Wesley
Hwang, Christine
Po, Michelle D.
Zhen, Mei [1 ]
机构
[1] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Dept Microbiol & Med Genet, Toronto, ON M5G 1X5, Canada
来源
DEVELOPMENT | 2007年 / 134卷 / 02期
关键词
sad-1; Neurabin; neuronal polarity; Caenorhabditis elegans;
D O I
10.1242/dev.02725
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The establishment of axon-dendrite identity in developing neurites is essential for the development of a functional nervous system. The SAD serine-threonine kinases have been implicated in regulating neuronal polarization and synapse formation. Here, we show that the C. elegans SAD-1 kinase regulates axonal identity and synapse formation through distinct mechanisms. We identified a scaffolding protein, Neurabin (NAB-1), as a physiological binding partner of SAD-1. Both sad-1 and nab-1 loss-of-function mutants display polarity defects in which synaptic vesicles accumulate in both axons and dendrites. We show that sad-1 and nab-1 function in the same genetic pathway to restrict axonal fate. Unlike sad-1, nab-1 mutants display normal morphology of vesicle clusters. Strikingly, although the physical interaction of NAB-1 with SAD-1 is necessary for polarity, it is dispensable for synapse morphology. We propose that Neurabin functions as a scaffold to facilitate SAD-1-mediated phosphorylation for substrates specific for restricting axonal fate during neuronal polarization.
引用
收藏
页码:237 / 249
页数:13
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