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蛋白酪氨酸磷酸酶-3促进SYD-2的分子内折叠，从而使神经元中的驱动蛋白-3 UNC-104失活。

PTP-3 phosphatase promotes intramolecular folding of SYD-2 to inactivate kinesin-3 UNC-104 in neurons.

作者信息

Muniesh Muthaiyan Shanmugam, Barmaver Syed Nooruzuha, Huang Hsin-Yi, Bayansan Odvogmed, Wagner Oliver Ingvar

机构信息

Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.

出版信息

Mol Biol Cell. 2020 Dec 15;31(26):2932-2947. doi: 10.1091/mbc.E19-10-0591. Epub 2020 Nov 4.

DOI:10.1091/mbc.E19-10-0591
PMID:33147118
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7927192/
Abstract

UNC-104 is the homolog of kinesin-3 KIF1A known for its fast shuffling of synaptic vesicle protein transport vesicles in axons. SYD-2 is the homolog of liprin-α in known to activate UNC-104; however, signals that trigger SYD-2 binding to the motor remain unknown. Because SYD-2 is a substrate of PTP-3/LAR PTPR, we speculate a role of this phosphatase in SYD-2-mediated motor activation. Indeed, coimmunoprecipitation assays revealed increased interaction between UNC-104 and SYD-2 in knockout worms. Intramolecular FRET analysis in living nematodes demonstrates that SYD-2 largely exists in an open conformation state in mutants. These assays also revealed that nonphosphorylatable SYD-2 (Y741F) exists predominately in folded conformations, while phosphomimicking SYD-2 (Y741E) primarily exists in open conformations. Increased UNC-104 motor clustering was observed along axons likely as a result of elevated SYD-2 scaffolding function mutants. Also, both motor velocities as well as cargo transport speeds were visibly increased in neurons of mutants. Lastly, epistatic analysis revealed that PTP-3 is upstream of SYD-2 to regulate its intramolecular folding.

摘要

UNC-104是驱动蛋白-3 KIF1A的同源物，以其在轴突中快速转运突触小泡蛋白运输小泡而闻名。SYD-2是已知能激活UNC-104的liprin-α的同源物；然而，触发SYD-2与该分子马达结合的信号仍不清楚。由于SYD-2是PTP-3/LAR PTPR的底物，我们推测这种磷酸酶在SYD-2介导的分子马达激活中发挥作用。事实上，免疫共沉淀分析显示在基因敲除线虫中UNC-104与SYD-2之间的相互作用增加。对线虫进行的分子内荧光共振能量转移分析表明，在突变体中SYD-2主要以开放构象状态存在。这些分析还表明，不可磷酸化的SYD-2（Y741F）主要以折叠构象存在，而模拟磷酸化的SYD-2（Y741E）主要以开放构象存在。在突变体中，由于SYD-2支架功能增强，观察到沿轴突的UNC-104分子马达聚集增加。此外，在突变体的神经元中，分子马达速度和货物运输速度均明显增加。最后，上位性分析表明PTP-3在SYD-2的上游调节其分子内折叠。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/b0b735a7be83/mbc-31-2932-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/933b091a1622/mbc-31-2932-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/a134c86327ea/mbc-31-2932-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/34b02a40a738/mbc-31-2932-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/584830dc4910/mbc-31-2932-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/843bbd215019/mbc-31-2932-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/cf8ab943d2df/mbc-31-2932-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/b0b735a7be83/mbc-31-2932-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/933b091a1622/mbc-31-2932-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/a134c86327ea/mbc-31-2932-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/34b02a40a738/mbc-31-2932-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/584830dc4910/mbc-31-2932-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/843bbd215019/mbc-31-2932-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/cf8ab943d2df/mbc-31-2932-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e08b/7927192/b0b735a7be83/mbc-31-2932-g007.jpg

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Int J Biol Sci. 2019 May 2;15(6):1125-1138. doi: 10.7150/ijbs.30543. eCollection 2019.
2
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Genetics. 2018 Nov;210(3):947-968. doi: 10.1534/genetics.118.301466.
3
Insights on UNC-104-dynein/dynactin interactions and their implications on axonal transport in Caenorhabditis elegans.
UNC-104 动力蛋白/动力蛋白激活蛋白复合物相互作用的新见解及其对秀丽隐杆线虫轴突运输的影响。
J Neurosci Res. 2019 Feb;97(2):185-201. doi: 10.1002/jnr.24339. Epub 2018 Oct 12.
4
The multiple functions of kinesin-4 family motor protein KIF4 and its clinical potential.驱动蛋白-4 家族运动蛋白 KIF4 的多种功能及其临床潜力。
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5
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6
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7
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8
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9
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10
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