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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >The neural cell adhesion molecule promotes maturation of the presynaptic endocytotic machinery by switching synaptic vesicle recycling from adaptor protein 3 (AP-3)- to AP-2-dependent mechanisms
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The neural cell adhesion molecule promotes maturation of the presynaptic endocytotic machinery by switching synaptic vesicle recycling from adaptor protein 3 (AP-3)- to AP-2-dependent mechanisms

机译:神经细胞粘附分子通过将突触小泡回收从衔接蛋白3(AP-3)-转换为AP-2依赖性机制来促进突触前内吞机制的成熟。

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摘要

Newly formed synapses undergo maturation during ontogenetic development via mechanisms that remain poorly understood. We show that maturation of the presynaptic endocytotic machinery in CNS neurons requires substitution of the adaptor protein 3 (AP-3) with AP-2 at the presynaptic plasma membrane. In mature synapses, AP-2 associates with the intracellular domain of the neural cell adhesion molecule (NCAM). NCAM promotes binding of AP-2 over binding of AP-3 to presynaptic membranes, thus favoring the substitution of AP-3 for AP-2 during formation of mature synapses. The presynaptic endocytotic machinery remains immature in adult NCAM-deficient (NCAM-/-) mice accumulating AP-3 instead of AP-2 and its partner protein AP180 in synaptic membranes and vesicles. NCAM deficiency or disruption of the NCAM/AP-2 complex in wild-type (NCAM+/+) neurons by overexpression of AP-2 binding-defective mutant NCAM interferes with efficient retrieval of the synaptic vesicle v-SNARE synaptobrevin 2. Abnormalities in synaptic vesicle endocytosis and recycling may thus contribute to neurological disorders associated with mutations in NCAM.
机译:新形成的突触通过尚不十分了解的机制在个体发育过程中经历成熟。我们显示中枢神经系统神经元的突触前内吞机制的成熟需要在突触前质膜上用AP-2替换衔接蛋白3(AP-3)。在成熟的突触中,AP-2与神经细胞粘附分子(NCAM)的胞内域相关。 NCAM促进AP-2的结合超过AP-3与突触前膜的结合,因此在成熟突触形成过程中有利于用AP-3取代AP-3。在成年的NCAM缺陷(NCAM-/-)小鼠中,突触前的胞吞机制仍然不成熟,它们在突触膜和囊泡中积聚AP-3而不是AP-2及其伴侣蛋白AP180。 AP-2结合缺陷型突变NCAM的过度表达导致NCAM缺乏或野生型(NCAM + / +)神经元中NCAM / AP-2复合物的破坏干扰了突触小泡v-SNARE突触小泡蛋白2的有效恢复。因此,囊泡内吞作用和再循环可能导致与NCAM突变相关的神经系统疾病。

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