Reticulon-like-1, the Drosophila orthologue of the hereditary spastic paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons.
Reticulon-like-1, the Drosophila orthologue of the hereditary spastic paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons.
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DOI：
10.1093/hmg/dds167
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发表时间：
2012-08-01
影响因子：
3.5
通讯作者：
O'Kane CJ
中科院分区：
文献类型：
--
作者：
O'Sullivan NC;Jahn TR;Reid E;O'Kane CJ
遗传性痉挛性截瘫的几个致病基因编码具有膜内发夹环的蛋白质，这些蛋白质有助于内质网(ER)的弯曲，但这一功能与轴突变性的相关性尚不清楚。其中一个基因是网状蛋白2。与哺乳动物相比，果蝇只有一个广泛表达的网状同源基因Rtnl1，因此我们用果蝇来测试它对内质网组织和轴突功能的重要性。Rtnl1分布与内质网重叠，但与粗面内质网不同，Rtnl1分布丰富于轴突。Rtnl1基因的缺失导致幼虫表皮粗面或片状ER的扩张和ER应激水平的升高。它还导致较长运动轴突远端及其突触前终末的异常，包括平滑内质网(SER)、微管细胞骨架和线粒体的破坏。相比之下，近端轴突部分似乎没有受到影响。我们的结果为远端较长轴突的SER的组织中的网状结构功能提供了直接证据，并支持了轴突SER受损可导致痉挛性截瘫的模型。我们的数据为进一步了解SER在轴突中的作用和该隔室受损的病理后果提供了一条途径。
Several causative genes for hereditary spastic paraplegia encode proteins with intramembrane hairpin loops that contribute to the curvature of the endoplasmic reticulum (ER), but the relevance of this function to axonal degeneration is not understood. One of these genes is reticulon2. In contrast to mammals, Drosophila has only one widely expressed reticulon orthologue, Rtnl1, and we therefore used Drosophila to test its importance for ER organization and axonal function. Rtnl1 distribution overlapped with that of the ER, but in contrast to the rough ER, was enriched in axons. The loss of Rtnl1 led to the expansion of the rough or sheet ER in larval epidermis and elevated levels of ER stress. It also caused abnormalities specifically within distal portions of longer motor axons and in their presynaptic terminals, including disruption of the smooth ER (SER), the microtubule cytoskeleton and mitochondria. In contrast, proximal axon portions appeared unaffected. Our results provide direct evidence for reticulon function in the organization of the SER in distal longer axons, and support a model in which spastic paraplegia can be caused by impairment of axonal the SER. Our data provide a route to further understanding of both the role of the SER in axons and the pathological consequences of the impairment of this compartment.
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DOI：
10.1083/jcb.200911024
发表时间：
2010-08-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Friedman JR;Webster BM;Mastronarde DN;Verhey KJ;Voeltz GK
通讯作者：
Voeltz GK
影响因子：
3
作者：
Jahn TR;Kohlhoff KJ;Scott M;Tartaglia GG;Lomas DA;Dobson CM;Vendruscolo M;Crowther DC
通讯作者：
Crowther DC
影响因子：
2.5
作者：
BROADWELL, RD;CATALDO, AM
通讯作者：
CATALDO, AM
影响因子：
4.7
作者：
Lu, JianPing;Rashid, Faiza;Byrne, Paula C.
通讯作者：
Byrne, Paula C.
影响因子：
3.3
作者：
HARTTER, DE;BURTON, PR;LAVERI, LA
通讯作者：
LAVERI, LA