Coordinated trafficking of synaptic vesicle and active zone proteins prior to synapse formation.
Coordinated trafficking of synaptic vesicle and active zone proteins prior to synapse formation.
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DOI：
10.1186/1749-8104-6-24
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发表时间：
2011-05-10
影响因子：
3.6
通讯作者：
Sabo SL
中科院分区：
文献类型：
--
作者：
Bury LA;Sabo SL
突触传递所需的蛋白质在新生突触中迅速组装，但这些蛋白质如何传递到发育中的突触前末端的机制尚不清楚。在突触形成之前，活性区蛋白和突触囊泡蛋白分别在不同的细胞器中沿着轴突运输，称为短笛-巴松管运输囊泡（PTVs）和突触囊泡蛋白运输囊泡（STVs）。虽然PTV和STV都被募集到轴突的同一位置，通常在轴突-树突接触的几分钟内，但在突触形成之前，PTV和STV的运输是否或如何协调尚不清楚。通过对同一轴突内PTVs和STVs动态的延时共聚焦成像，我们发现囊泡运输至少通过两种机制进行协调。首先，在形成稳定的终端之前，有相当比例的stv和ptv一起运输。其次，单独的ptv和stv在轴突内共享暂停位点。重要的是，对于stv和ptv来说，遇到另一种类型的囊泡会增加它们暂停的倾向。为了确定PTV- stv相互作用是否对暂停很重要，通过表达与syntabulin的syntaxin结合域相对应的显性负结构体，PTV密度在轴突中降低，该结构体将PTV与其KIF5B马达连接起来。这种ptv的减少对STV暂停和移动的影响很小，这表明STV和ptv之间的相互作用并不是STV暂停增强的原因。我们的研究结果表明，stv和ptv的贩运甚至在突触发育之前就已经协调。这种转运和暂停的新协调可能提供了一种机制，通过这种机制，突触前末端的所有成分都可以在突触形成的位点迅速积累。
The proteins required for synaptic transmission are rapidly assembled at nascent synapses, but the mechanisms through which these proteins are delivered to developing presynaptic terminals are not understood. Prior to synapse formation, active zone proteins and synaptic vesicle proteins are transported along axons in distinct organelles referred to as piccolo-bassoon transport vesicles (PTVs) and synaptic vesicle protein transport vesicles (STVs), respectively. Although both PTVs and STVs are recruited to the same site in the axon, often within minutes of axo-dendritic contact, it is not known whether or how PTV and STV trafficking is coordinated before synapse formation. Here, using time-lapse confocal imaging of the dynamics of PTVs and STVs in the same axon, we show that vesicle trafficking is coordinated through at least two mechanisms. First, a significant proportion of STVs and PTVs are transported together before forming a stable terminal. Second, individual PTVs and STVs share pause sites within the axon. Importantly, for both STVs and PTVs, encountering the other type of vesicle increases their propensity to pause. To determine if PTV-STV interactions are important for pausing, PTV density was reduced in axons by expression of a dominant negative construct corresponding to the syntaxin binding domain of syntabulin, which links PTVs with their KIF5B motor. This reduction in PTVs had a minimal effect on STV pausing and movement, suggesting that an interaction between STVs and PTVs is not responsible for enhancing STV pausing. Our results indicate that trafficking of STVs and PTVs is coordinated even prior to synapse development. This novel coordination of transport and pausing might provide mechanisms through which all of the components of a presynaptic terminal can be rapidly accumulated at sites of synapse formation.
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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：
7.5
作者：
Chavrier, P;Goud, B
通讯作者：
Goud, B
影响因子：
25
作者：
Sabo, SL;McAllister, AK
通讯作者：
McAllister, AK
影响因子：
5.3
作者：
Ruthazer, ES;Li, JL;Cline, HT
通讯作者：
Cline, HT
影响因子：
3.5
作者：
Dresbach, T;Hempelmann, A;Gundelfinger, ED
通讯作者：
Gundelfinger, ED