Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17.
Coupled Control of Distal Axon Integrity and Somal Responses to Axonal Damage by the Palmitoyl Acyltransferase ZDHHC17.
复制标题
棕榈酰酰基转移酶ZDHHC17对远端轴突完整性和轴突损伤的体细胞反应的耦合控制。
DOI：
10.1016/j.celrep.2020.108365
复制
发表时间：
2020-11-17
期刊：
影响因子：
8.8
通讯作者：
Thomas GM
中科院分区：
文献类型：
--
作者：
Niu J;Sanders SS;Jeong HK;Holland SM;Sun Y;Collura KM;Hernandez LM;Huang H;Hayden MR;Smith GM;Hu Y;Jin Y;Thomas GM
视神经夹伤后，多数视网膜神经节细胞(RGC)胞体和远端轴突变性。RGC胞体和远端轴突退行性变以前被认为是由两条平行的途径控制的，分别涉及激酶双亮氨酸拉链激酶(DLK)的激活和轴突存活因子烟酰胺单核苷酸腺苷转移酶-2(NMNA2)的缺失。在这里，我们报告了DLK和NMNA2被棕榈酰酰基转移酶ZDHHC17棕榈酰化偶联这些信号。ZDHHC17依赖的棕榈酰化使ONC后依赖DLK的胞体变性，也确保了健康视神经中依赖NMNAT的远端轴突的完整性。我们提供的证据表明，ZDHHC17还控制着背根神经节(DRG)神经元的生存与退化决定，并在NMNA2和DLK中发现了控制其ZDHHC17依赖调控的保守基序。这些发现表明，躯体和远端轴突完整性的控制应被认为是一个单一的、整体的过程，由两条棕榈酰化依赖的通路协同作用介导。牛等人。结果表明，ZDHHC17棕榈酰化DLK，轴突到胞体前退变信号的中介，以及NMNA2，一种生存因子，其损伤后的快速丢失触发远端轴突退变。ZDHHC17对这两个关键蛋白的棕榈酰化反应确保了远端轴突和神经元胞体对轴突损伤的协调反应。
After optic nerve crush (ONC), the cell bodies and distal axons of most retinal ganglion cells (RGCs) degenerate. RGC somal and distal axon degenerations were previously thought to be controlled by two parallel pathways, involving activation of the kinase dual leucine-zipper kinase (DLK) and loss of the axon survival factor nicotinamide mononucleotide adenylyltransferase-2 (NMNAT2), respectively. Here, we report that palmitoylation of both DLK and NMNAT2 by the palmitoyl acyltransferase ZDHHC17 couples these signals. ZDHHC17-dependent palmitoylation enables DLK-dependent somal degeneration after ONC and also ensures NMNAT-dependent distal axon integrity in healthy optic nerves. We provide evidence that ZDHHC17 also controls survival-versus-degeneration decisions in dorsal root ganglion (DRG) neurons, and we identify conserved motifs in NMNAT2 and DLK that govern their ZDHHC17-dependent regulation. These findings suggest that the control of somal and distal axon integrity should be considered as a single, holistic process, mediated by the concerted action of two palmitoylation-dependent pathways. Niu et al. show that ZDHHC17 palmitoylates DLK, a mediator of axon-to-soma pro-degenerative signaling, and also NMNAT2, a survival factor whose rapid loss post-injury triggers distal axon degeneration. Palmitoylation of these two key proteins by ZDHHC17 ensures a coordinated response of distal axons and neuronal somas to axonal injury.
登录
查看更多内容
影响因子：
6.1
作者：
Fernandes, Kimberly A.;Harder, Jeffrey M.;Fornarola, Laura B.;Freeman, Robert S.;Clark, Abbot F.;Pang, Iok-Hou;John, Simon W. M.;Libby, Richard T.
通讯作者：
Libby, Richard T.
影响因子：
4.4
作者：
Edmonds MJ;Morgan A
通讯作者：
Morgan A
影响因子：
11.8
作者：
Ernst AM;Syed SA;Zaki O;Bottanelli F;Zheng H;Hacke M;Xi Z;Rivera-Molina F;Graham M;Rebane AA;Björkholm P;Baddeley D;Toomre D;Pincet F;Rothman JE
通讯作者：
Rothman JE
影响因子：
16.2
作者：
Fernández-Chacón, R;Wölfel, M;Südhof, TC
通讯作者：
Südhof, TC
影响因子：
4.8
作者：
Collura, Kaitlin M.;Niu, Jingwen;Thomas, Gareth M.
通讯作者：
Thomas, Gareth M.