Presynaptic Biogenesis Requires Axonal Transport of Lysosome-Related Vesicles

Vukoja Anela; Rey Ulises; Petzoldt Astrid G.; Ott Christoph; Vollweiter Dennis; Quentin Christine; Puchkov Dymtro; Reynolds Eric; Lehmann Martin; Hohensee Svea; Rosa Stefanie; Lipowsky Reinhard; Sigrist Stephan J.; Haucke Volker

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Presynaptic Biogenesis Requires Axonal Transport of Lysosome-Related Vesicles

机译：突触前生物生成需要溶酶体相关囊泡的轴突运输

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Nervous system function relies on the polarized architecture of neurons, established by directional transport of pre-and postsynaptic cargoes. While delivery of postsynaptic components depends on the secretory pathway, the identity of the membrane compartment(s) supplying presynaptic active zone (AZ) and synaptic vesicle (SV) proteins is unclear. Live imaging in Drosophila larvae and mouse hippocampal neurons provides evidence that presynaptic biogenesis depends on axonal co-transport of SV and AZ proteins in presynaptic lysosome-related vesicles (PLVs). Loss of the lysosomal kinesin adaptor Arl8 results in the accumulation of SV- and AZ-protein-containing vesicles in neuronal cell bodies and a corresponding depletion of SV and AZ components from presynaptic sites, leading to impaired neurotransmission. Conversely, presynaptic function is facilitated upon overexpression of Arl8. Our data reveal an unexpected function for a lysosome-related organelle as an important building block for presynaptic biogenesis.

机译：神经系统函数依赖于神经元的极化结构，由前后货物的定向运输建立。虽然延伸性组分的递送取决于分泌途径，但供应突触前有源区（AZ）和突触囊泡（SV）蛋白的膜隔室的同一性尚不清楚。在果蝇幼虫和小鼠海马神经元的实时成像提供了证据，即突触前生物发生取决于突触前溶酶体相关的囊泡（PLVS）中的SV和AZ蛋白的轴突交通。溶酶体Kinesin适配器ARL8的损失导致神经元细胞体中的含SV和AZ蛋白质的囊泡的积累和来自突触前位点的SV和AZ组分的相应耗竭，导致神经递质受损。相反，在ARL8的过度表达时促进了突触前功能。我们的数据揭示了溶酶体相关细胞器的意外功能，作为突触前生物发生的重要构建块。

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《Neuron》 |2018年第6期|共24页
作者
Vukoja Anela; Rey Ulises; Petzoldt Astrid G.; Ott Christoph; Vollweiter Dennis; Quentin Christine; Puchkov Dymtro; Reynolds Eric; Lehmann Martin; Hohensee Svea; Rosa Stefanie; Lipowsky Reinhard; Sigrist Stephan J.; Haucke Volker;
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Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

Free Univ Berlin Fac Biol Chem Pharm D-14195 Berlin Germany;

Free Univ Berlin Fac Biol Chem Pharm D-14195 Berlin Germany;

Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

Free Univ Berlin Fac Biol Chem Pharm D-14195 Berlin Germany;

Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

Free Univ Berlin Fac Biol Chem Pharm D-14195 Berlin Germany;

Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

Max Planck Inst Colloids &

Interfaces D-14476 Potsdam Germany;

Free Univ Berlin Fac Biol Chem Pharm D-14195 Berlin Germany;

Leibniz Forschungsinst Mol Pharmakol FMP D-13125 Berlin Germany;

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正文语种 eng
中图分类神经病学;
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专利

1. Presynaptic Biogenesis Requires Axonal Transport of Lysosome-Related Vesicles [J] . Vukoja Anela, Rey Ulises, Petzoldt Astrid G., Neuron . 2018,第6期

机译：突触前生物生成需要溶酶体相关囊泡的轴突运输
2. An Arf-like small G protein, ARL-8, promotes the axonal transport of presynaptic cargoes by suppressing vesicle aggregation. [J] . Klassen MP, Wu YE, Maeder CI, Neuron . 2010,第5期

机译：Arf样小G蛋白ARL-8通过抑制囊泡聚集来促进突触前货物的轴突运输。
3. Fast Vesicle Transport Is Required for the Slow Axonal Transport of Synapsin (vol 33, pg 15362, 2013) [J] . Tang Yong, Scott David, Das Utpal, The Journal of Neuroscience: The Official Journal of the Society for Neuroscience . 2019,第28期

机译：Synapsin缓慢的轴突运输需要快速囊泡运输（Vol 33，PG 15362,2013）
4. MODELING THE EFFECT OF VESICLE TRAPS ON MASS TRANSFER AND TRAFFIC JAM FORMATION IN FAST AXONAL TRANSPORT [C] . Andrey V. Kuznetsov ASME international heat transfer conference;IHTC14 . 2011

机译：在快速轴突运输中模拟交通陷阱对交通运输和交通堵塞形成的影响
5. Physical changes in macromolecules of active zone material that regulate docking and fusion of synaptic vesicle membrane with the presynaptic membrane and the removal of fused vesicle membrane from the active zone. [D] . Jung, Jae Hoon. 2009

机译：活性区材料大分子的物理变化，可调节突触小泡膜与突触前膜的对接和融合以及从活性区去除融合的小泡膜。
6. Biogenesis of Lysosome-related Organelles Complex-1 Subunit 1 (BLOS1) Interacts with Sorting Nexin 2 and the Endosomal Sorting Complex Required for Transport-I (ESCRT-I) Component TSG101 to Mediate the Sorting of Epidermal Growth Factor Receptor into Endosomal Compartments [O] . Aili Zhang, Xin He, Ling Zhang, 2014

机译：溶酶体相关的细胞器复合物1亚基1（BLOS1）的生物发生与分选Nexin 2和运输-I（ESCRT-I）组分TSG101介导将表皮生长因子受体的分选介导进入内膜隔室所需的内体分选复合物相互作用
7. Biogenesis of lysosome-related organelles complex-1 subunit 1 (BLOS1) interacts with sorting nexin 2 and the endosomal sorting complex required for transport-I (ESCRT-I) component TSG101 to mediate the sorting of epidermal growth factor receptor into endosomal compartments. [O] . Zhang, Aili, He, Xin, Zhang, Ling, 2014

机译：溶酶体相关细胞器复合物-1亚基1（BLOs1）的生物发生与分选nexin 2和运输-I（EsCRT-I）组分TsG101所需的内体分选复合物相互作用，以介导将表皮生长因子受体分选成内体区室。

Presynaptic Biogenesis Requires Axonal Transport of Lysosome-Related Vesicles

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