UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes.
UNC-16/JIP3 regulates early events in synaptic vesicle protein trafficking via LRK-1/LRRK2 and AP complexes.
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DOI：
10.1371/journal.pgen.1007100
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发表时间：
2017-11
期刊：
影响因子：
4.5
通讯作者：
Koushika SP
中科院分区：
文献类型：
--
作者：
Choudhary B;Kamak M;Ratnakaran N;Kumar J;Awasthi A;Li C;Nguyen K;Matsumoto K;Hisamoto N;Koushika SP
JIP 3/dSYD是一种MAPK-支架蛋白，在蛋白质运输中起作用。我们发现，它是存在于高尔基体和突触囊泡蛋白（SVP）和树突状蛋白在神经元中的极化分布是必要的。CYP-16将高尔基体酶从SVP转运载体中排除，并促进将特定SVP包含到相同的转运载体中。SVP的运输作用的UNC-16介导的LRK-1，其本地化的高尔基体减少unc-16动物。通过LRK-1，AP-16还使AP-1复合物的μ亚基能够高尔基体定位。AP 1调节SVP转运载体的大小，但不调节其组成。此外，通过AP-3复合物，ERK-16和LRK-1调节SVP转运载体的组成，但不调节其大小。这些早期的生物发生步骤对于依赖突触囊泡马达、轴突运输的α-104是必不可少的。我们的研究结果表明，在高尔基体和/或后高尔基体室，以控制SV的生物合成的早期步骤，ESTA-16及其下游效应，LRK-1和AP复合物的功能。依赖于β-16的排斥、包含和运动募集步骤对于神经元货物的极化分布至关重要。突触囊泡（SV）在突触处具有确定的组成和大小。在这些囊泡膜上发现的多种突触囊泡蛋白（SVP）在不同的运输载体中在细胞体处合成并运输出细胞体。然而，我们还不了解不同的SVP如何被排序并传输到突触。我们发现，在一系列重要步骤中，JNK-16/JIP 3起着关键作用，以确保适当的膜组成和随后的SVP载体离开细胞体的大小。这些过程是“排除”常驻高尔基体酶，然后在同一运输载体中“包含”突触囊泡蛋白。调节的组成和大小似乎发生彼此独立，并依赖于两个不同的AP复合物下游LRK-1的作用。我们的研究进一步表明，所形成的运输载体的组合物是重要的招聘电机，从而为极化本地化的SVPs。
JIP3/UNC-16/dSYD is a MAPK-scaffolding protein with roles in protein trafficking. We show that it is present on the Golgi and is necessary for the polarized distribution of synaptic vesicle proteins (SVPs) and dendritic proteins in neurons. UNC-16 excludes Golgi enzymes from SVP transport carriers and facilitates inclusion of specific SVPs into the same transport carrier. The SVP trafficking roles of UNC-16 are mediated through LRK-1, whose localization to the Golgi is reduced in unc-16 animals. UNC-16, through LRK-1, also enables Golgi-localization of the μ-subunit of the AP-1 complex. AP1 regulates the size but not the composition of SVP transport carriers. Additionally, UNC-16 and LRK-1 through the AP-3 complex regulates the composition but not the size of the SVP transport carrier. These early biogenesis steps are essential for dependence on the synaptic vesicle motor, UNC-104 for axonal transport. Our results show that UNC-16 and its downstream effectors, LRK-1 and the AP complexes function at the Golgi and/or post-Golgi compartments to control early steps of SV biogenesis. The UNC-16 dependent steps of exclusion, inclusion and motor recruitment are critical for polarized distribution of neuronal cargo. Synaptic vesicles (SVs) have a defined composition and size at the synapse. The multiple synaptic vesicle proteins (SVPs) found on these vesicle membranes are synthesized at and trafficked out of the cell body in distinct transport carriers. However, we do not yet understand how different SVPs are sorted and trafficked to the synapse. We show that UNC-16/JIP3 plays a critical role, in a series of essential steps, to ensure proper membrane composition and size of the ensuing SVP carrier exiting the cell body. These processes are “exclusion” of resident Golgi enzymes followed by the “inclusion” of synaptic vesicle proteins in the same transport carrier. Regulation of composition and size seems to occur independently of each other and depends on two distinct AP complexes acting downstream to LRK-1. Our study further indicates that the composition of the transport carrier formed is important for the recruitment of motors and consequently for the polarized localization of SVPs.
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影响因子：
16.2
作者：
Klassen, Matthew P.;Wu, Ye E.;Maeder, Celine I.;Nakae, Isei;Cueva, Juan G.;Lehrman, Emily K.;Tada, Minoru;Gengyo-Ando, Keiko;Wang, George J.;Goodman, Miriam;Mitani, Shohei;Kontani, Kenji;Katada, Toshiaki;Shen, Kang
通讯作者：
Shen, Kang
影响因子：
3.3
作者：
Edwards, Stacey L.;Morrison, Logan M.;Miller, Kenneth G.
通讯作者：
Miller, Kenneth G.
影响因子：
11.4
作者：
EDELMANN, L;HANSON, PI;JAHN, R
通讯作者：
JAHN, R
影响因子：
64.5
作者：
Bowman, AB;Kamal, A;Goldstein, LSB
通讯作者：
Goldstein, LSB
影响因子：
56.9
作者：
Bellocchio, EE;Reimer, RJ;Edwards, RH
通讯作者：
Edwards, RH