Lack of a Retinal Phenotype in a Syne-2/Nesprin-2 Knockout Mouse Model
Lack of a Retinal Phenotype in a Syne-2/Nesprin-2 Knockout Mouse Model
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DOI：
10.3390/cells8101238
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发表时间：
2019-10-01
期刊：
影响因子：
6
通讯作者：
Giessl, Andreas
中科院分区：
文献类型：
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作者：
Falk, Nathalie;Joachimsthaler, Anneka;Giessl, Andreas
Syne-2（也称为Nesprin-2）是主要在外核膜以及其他亚细胞区室中发现的蛋白质家族的成员。Syne-2含有C-末端KASH跨膜结构域，并且是通过结合肌动蛋白丝将核被膜与细胞骨架相关联的蛋白质网络的一部分。Syne-2在视网膜发育过程中的核迁移、核定位和纤毛发生中起作用。在之前的研究中，我们发现了Syne-2和多功能支架蛋白Pericentrin（Pcnt）之间的联系。Syne-2和Pcnt的相互作用的消除显示在视网膜发育过程中的核迁移和外段的形成中的缺陷，以及在纤毛发生开始时的中心体迁移中的干扰。在本研究中，分析了特别关注Pcnt和纤毛发生的Syne-2 KO小鼠模型Nesprin-2 oABD（Syne-2（tm 1 Ngl），MGI）。我们发现Syne-2 KO小鼠视网膜中Syne-2的表达减少，但没有发现显著的结构表型，只有一个较小的功能表型。第一次，详细的表达分析显示在Syne-2/Nesprin-2 KO小鼠中大于400 kDa（类似于750 kDa）的Syne-2蛋白的表达。总之，在Syne-2/Nesprin-2 KO小鼠中缺乏明显的表型表明使用替代翻译起始位点，产生具有完整Pcnt相互作用位点的Syne-2剪接变体。然而，在Syne-2/Nesprin-2 KO小鼠中的肌动蛋白结合位点的缺失揭示了暗视振荡电位的高度可变性，假设Syne-2在同步视网膜内过程中的新功能。
Syne-2 (also known as Nesprin-2) is a member of a family of proteins that are found primarily in the outer nuclear membrane, as well as other subcellular compartments. Syne-2 contains a C-terminal KASH transmembrane domain and is part of a protein network that associates the nuclear envelope to the cytoskeleton via the binding to actin filaments. Syne-2 plays a role in nuclear migration, nuclear positioning during retinal development, and in ciliogenesis. In a previous study, we showed a connection between Syne-2 and the multifunctional scaffold protein Pericentrin (Pcnt). The elimination of the interaction of Syne-2 and Pcnt showed defects in nuclear migration and the formation of outer segments during retinal development, as well as disturbances in centrosomal migration at the beginning of ciliogenesis in general. In this study, the Syne-2 KO mouse model Nesprin-2oABD (Syne-2(tm1Ngl), MGI) with special attention to Pcnt and ciliogenesis was analyzed. We show reduced expression of Syne-2 in the retina of the Syne-2 KO mouse but found no significant structural-and only a minor functional-phenotype. For the first time, detailed expression analyses showed an expression of a Syne-2 protein larger than 400 kDa (similar to 750 kDa) in the Syne-2/Nesprin-2 KO mouse. In conclusion, the lack of an overt phenotype in Syne-2/Nesprin-2 KO mice suggests the usage of alternative translational start sites, producing Syne-2 splice variants with an intact Pcnt interaction site. Nevertheless, deletion of the actin-binding site in the Syne-2/Nesprin-2 KO mouse revealed a high variability in scotopic oscillatory potentials assuming a novel function of Syne-2 in synchronizing inner retinal processes.