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外显肽 70 对于热应激下的轴突延伸和存活是必需的。

Exo70 Is Essential for Neurite Extension and Survival under Thermal Stress.

机构信息

Laboratory of Drosophila Research.

Biochemistry Program.

出版信息

J Neurosci. 2018 Sep 12;38(37):8071-8086. doi: 10.1523/JNEUROSCI.0620-18.2018. Epub 2018 Aug 1.

Abstract

The octomeric exocyst complex governs the final step of exocytosis in both plants and animals. Its roles, however, extend beyond exocytosis and include organelle biogenesis, ciliogenesis, cell migration, and cell growth. Exo70 is a conserved component of the exocyst whose function in is unclear. In this study, we characterized two mutant alleles of mutants exhibit reduced synaptic growth, locomotor activity, glutamate receptor density, and mEPSP amplitude. We found that presynaptic Exo70 is necessary for normal synaptic growth at the neuromuscular junction (NMJ). At the neuromuscular junction, genetically interacts with the small GTPase to regulate synaptic growth. Loss of Exo70 leads to the blockage of JNK signaling-, activity-, and temperature-induced synaptic outgrowths. We showed that this phenotype is associated with an impairment of integral membrane protein transport to the cell surface at synaptic terminals. In octopaminergic motor neurons, Exo70 is detected in synaptic varicosities, as well as the regions of membrane extensions in response to activity stimulation. Strikingly, mild thermal stress causes severe neurite outgrowth defects and pharate adult lethality in mutants. mutants also display defective locomotor activity in response to starvation stress. These results demonstrated that Exo70 is an important regulator of induced synaptic growth and is crucial for an organism's adaptation to environmental changes. The exocyst complex is a conserved protein complex directing secretory vesicles to the site of membrane fusion during exocytosis, which is essential for transporting proteins and membranes to the cell surface. Exo70 is a subunit of the exocyst complex whose roles in neurons remain elusive, and its function in is unclear. In , Exo70 is expressed in both glutamatergic and octopaminergic neurons, and presynaptic Exo70 regulates synaptic outgrowth. Moreover, mutants have impaired integral membrane transport to the cell surface at synaptic terminals and block several kinds of induced synaptic growth. Remarkably, elevated temperature causes severe arborization defects and lethality in mutants, thus underpinning the importance of Exo70 functions in development and adaptation to the environment.

摘要

八聚体外泌体复合物在动植物的胞吐作用的最后一步中起作用。然而,其作用不仅限于胞吐作用,还包括细胞器发生、纤毛发生、细胞迁移和细胞生长。Exo70 是外泌体的保守组成部分,其在 中的功能尚不清楚。在这项研究中,我们描述了 两个突变等位基因的特征; 突变体表现出突触生长、运动活性、谷氨酸受体密度和 mEPSP 幅度降低。我们发现,突触前 Exo70 对于神经肌肉接头 (NMJ) 中的正常突触生长是必需的。在神经肌肉接头处, 与小 GTPase 相互作用以调节突触生长。Exo70 的缺失导致 JNK 信号转导、活性和温度诱导的突触生长受阻。我们表明,这种表型与突触末端完整膜蛋白向细胞表面的运输受损有关。在章鱼胺运动神经元中,Exo70 检测到突触小泡中以及响应活动刺激的膜延伸区域。引人注目的是,轻度热应激会导致 突变体严重的神经突生长缺陷和假成虫致死。 突变体在响应饥饿应激时也表现出运动活性缺陷。这些结果表明,Exo70 是诱导突触生长的重要调节剂,对于生物体适应环境变化至关重要。外泌体复合物是一种保守的蛋白质复合物,在胞吐作用过程中指导分泌囊泡到达膜融合部位,对于将蛋白质和膜运输到细胞表面至关重要。Exo70 是外泌体复合物的一个亚基,其在神经元中的作用仍不清楚,其在 中的功能也不清楚。在 中,Exo70 在谷氨酸能和章鱼胺能神经元中表达,并且突触前 Exo70 调节突触生长。此外, 突变体在突触末端的完整膜运输到细胞表面受损,并阻断几种诱导的突触生长。值得注意的是,高温会导致 突变体严重的分支缺陷和致死性,从而强调了 Exo70 功能在发育和适应环境中的重要性。

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