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Neurexin and frizzled intercept axonal transport at microtubule minus ends to control synapse formation
Developmental Cell ( IF 10.7 ) Pub Date : 2022-07-08 , DOI: 10.1016/j.devcel.2022.06.009
Santiago Balseiro-Gómez 1 , Junhyun Park 1 , Yang Yue 2 , Chen Ding 3 , Lin Shao 1 , Selim Ҫetinkaya 1 , Caroline Kuzoian 1 , Marc Hammarlund 3 , Kristen J Verhey 2 , Shaul Yogev 1
Affiliation  

Synapse formation is locally determined by transmembrane proteins, yet synaptic material is synthesized remotely and undergoes processive transport in axons. How local synaptogenic signals intercept synaptic cargo in transport to promote its delivery and synapse formation is unknown. We found that the control of synaptic cargo delivery at microtubule (MT) minus ends mediates pro- and anti-synaptogenic activities of presynaptic neurexin and frizzled in C. elegans and identified the atypical kinesin VAB-8/KIF26 as a key molecule in this process. VAB-8/KIF26 levels at synaptic MT minus ends are controlled by frizzled and neurexin; loss of VAB-8 mimics neurexin mutants or frizzled hyperactivation, and its overexpression can rescue synapse loss in these backgrounds. VAB-8/KIF26 is required for the synaptic localization of other minus-end proteins and promotes the pausing of retrograde transport to allow delivery to synapses. Consistently, reducing retrograde transport rescues synapse loss in vab-8 and neurexin mutants. These results uncover a mechanistic link between synaptogenic signaling and axonal transport.



中文翻译:


神经毒素和卷曲在微管负端拦截轴突运输以控制突触形成



突触形成是由跨膜蛋白局部决定的,但突触物质是远程合成的,并在轴突中进行过程运输。局部突触信号如何拦截运输中的突触货物以促进其传递和突触形成尚不清楚。我们发现,在秀丽隐杆线虫中,微管(MT)负端突触货物传递的控制介导突触前神经素和卷曲的促突触发生和抗突触发生活性,并确定非典型驱动蛋白 VAB-8/KIF26 是该过程中的关键分子。突触 MT 负端的 VAB-8/KIF26 水平由卷曲蛋白和神经毒素控制; VAB-8 的缺失模拟神经毒素突变体或卷曲过度激活,其过度表达可以挽救这些背景下的突触缺失。 VAB-8/KIF26 是其他负端蛋白突触定位所必需的,并促进逆行运输暂停以允许递送至突触。一致地,减少逆行运输可以挽救vab-8和 neurexin 突变体的突触损失。这些结果揭示了突触信号传导和轴突运输之间的机制联系。

更新日期:2022-07-08
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