BIG1/Arfgef1 and Arf1 regulate the initiation of myelination by Schwann cells in mice.
BIG1/Arfgef1 and Arf1 regulate the initiation of myelination by Schwann cells in mice.
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DOI：
10.1126/sciadv.aar4471
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发表时间：
2018-04
期刊：
影响因子：
13.6
通讯作者：
Yamauchi J
中科院分区：
文献类型：
--
作者：
Miyamoto Y;Torii T;Tago K;Tanoue A;Takashima S;Yamauchi J
BIG 1及其效应子Arf 1是新近加入到控制轴突髓鞘形成的信号分子列表中的。在哺乳动物的周围神经系统发育过程中，许旺细胞将其质膜包裹在神经元轴突周围，形成多个髓鞘。成熟的髓鞘隔离轴突并增加神经传导速度，同时保护神经纤维免受各种应力，如物理应力。尽管这种功能的重要性，在髓鞘形成的动态形态变化的分子单位没有得到充分的理解。Arf 1是一种小的鸟苷三磷酸结合蛋白，在细胞内运输和相关信号传导中发挥多种作用，这两种过程都参与细胞形态发生。我们证明，Arf 1鸟嘌呤核苷酸交换因子，布雷菲德菌素A抑制鸟嘌呤核苷酸交换蛋白1（BIG 1）/Arfgef 1，和效应Arf 1调节启动髓鞘的轴突许旺细胞。雪旺细胞特异性BIG 1条件性敲除小鼠，这已经产生了这里，表现出减少髓鞘厚度和髓鞘蛋白零在髓鞘膜中的定位减少，与他们的同窝对照。BIG 1敲除小鼠神经特异性地减少AP 1网格蛋白衔接蛋白亚基中Arf 1的量，但不减少Arf 1与GGA 1（高尔基体定位的，含γ-衔接蛋白耳的，Arf结合蛋白1）转运蛋白的结合。在COPI外被体蛋白亚基中Arf 1的量在敲除小鼠和对照中是相当的。在Arf 1条件性基因敲除小鼠中观察到髓鞘厚度的类似结果，这些小鼠也是在这里产生的。因此，BIG 1和Arf 1单位在许旺细胞髓鞘形成中起关键作用，将其新添加到控制髓鞘形成的分子单位列表中。
BIG1 and its effector Arf1 are newly added to the list of signaling molecules controlling axonal myelination. During development of the peripheral nervous system in mammals, Schwann cells wrap their plasma membranes around neuronal axons, forming multiple myelin sheaths. A mature myelin sheath insulates axons and increases nerve conduction velocity while protecting nerve fibers from various stresses such as physical ones. Despite this functional importance, the molecular units that underlie dynamic morphological changes in formation of myelin sheaths are not sufficiently understood. Arf1 is a small guanosine triphosphate–binding protein that plays multiple roles in intracellular trafficking and related signaling, both of which are processes involved in cell morphogenesis. We demonstrate that the Arf1 guanine nucleotide exchange factor, brefeldin A–inhibited guanine nucleotide-exchange protein 1 (BIG1)/Arfgef1, and the effector Arf1 regulate the initiation of myelination of axons by Schwann cells. Schwann cell–specific BIG1 conditional knockout mice, which have been generated here, exhibit reduced myelin thickness and decreased localization of myelin protein zero in the myelin membrane, compared with their littermate controls. BIG1 knockout mouse nerves specifically decrease the amounts of Arf1 in the AP1 clathrin adaptor protein subunits but not the Arf1 binding to GGA1 (Golgi-localized, gamma-adaptin ear-containing, Arf-binding protein 1) transporting proteins. The amounts of Arf1 in the COPI coatomer protein subunits were comparable in the knockout mice and controls. Similar results in myelin thickness are observed in Arf1 conditional knockout mice, which have also been generated here. Thus, the BIG1 and Arf1 unit plays a key role in Schwann cell myelination, newly adding it to the list of molecular units controlling myelination.
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影响因子：
64.5
作者：
Ren X;Farías GG;Canagarajah BJ;Bonifacino JS;Hurley JH
通讯作者：
Hurley JH
影响因子：
14.8
作者：
Saenz, Jose B.;Sun, William J.;Chang, Jae Won;Li, Jinmei;Bursulaya, Badry;Gray, Nathanael S.;Haslam, David B.
通讯作者：
Haslam, David B.
DOI：
10.1083/jcb.201310021
发表时间：
2014-01-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bonifacino JS
通讯作者：
Bonifacino JS
影响因子：
30.8
作者：
Sheen, VL;Ganesh, VS;Walsh, CA
通讯作者：
Walsh, CA
DOI：
10.1038/nrm3117
发表时间：
2011-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
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