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SORLA Expression in Synaptic Plexiform Layers of Mouse Retina.
Molecular Neurobiology ( IF 5.1 ) Pub Date : 2020-05-29 , DOI: 10.1007/s12035-020-01946-x
Giulia Monti 1 , Marianne L Jensen 1 , Arnela Mehmedbasic 1 , Margarita Melnikova Jørgensen 2, 3 , Ida E Holm 2, 3 , Pernille Barkholt 1 , Egija Zole 1 , Christian B Vægter 1 , Henrik Vorum 4 , Jens R Nyengaard 5 , Olav M Andersen 1
Affiliation  

Sorting protein–related receptor containing LDLR class A repeats (SORLA; also known as LR11) exerts intraneuronal trafficking functions in the central nervous system. Recently, involvement of SORLA in retinogenesis was proposed, but no studies have examined yet in detail the expression pattern of this sorting receptor in the retina. Here, we provide a spatio-temporal characterization of SORL1 mRNA and its translational product SORLA in the postnatal mouse retina. Using stereological analysis, we confirmed previous studies showing that receptor depletion in knockout mice significantly reduces the number of cells in the inner nuclear layer (INL), suggesting that functional SORLA expression is essential for the development of this retinal strata. qPCR and Western blot analyses showed that SORL1/SORLA expression peaks at postnatal day 15, just after eye opening. Interestingly, we found that transcripts are somatically located in several neuronal populations residing in the INL and the ganglion cell layer, whereas SORLA protein is also present in the synaptic plexiform layers. In line with receptor expression in dendritic terminals, we found delayed stratification of the inner plexiform layer in knockout mice, indicating an involvement of SORLA in neuronal connectivity. Altogether, these data suggest a novel role of SORLA in synaptogenesis. Receptor dysfunctions may be implicated in morphological and functional impairments of retinal inner layer formation associated with eye disorders.



中文翻译:

SORLA在小鼠视网膜突触突触状层中的表达。

包含LDLR A类重复序列的蛋白质相关受体的分类(SORLA;也称为LR11)在中枢神经系统中发挥神经内运输功能。最近,提出了SORLA参与视网膜发生的研究,但是尚无研究详细检查这种分选受体在视网膜中的表达模式。在这里,我们提供了出生后小鼠视网膜中SORL1 mRNA及其翻译产物SORLA的时空特征。使用立体分析,我们证实了先前的研究,这些研究表明,基因敲除小鼠的受体耗竭显着减少了内核层(INL)中的细胞数量,表明功能性SORLA表达对于视网膜层的发育至关重要。qPCR和Western blot分析表明SORL1/ SORLA表达在产后第15天达到峰值,就在睁开眼睛之后。有趣的是,我们发现转录本位于体细胞中位于INL和神经节细胞层中的几个神经元群体中,而SORLA蛋白也存在于突触丛状层中。与树突状末端中的受体表达一致,我们发现基因敲除小鼠的内部丛状层延迟分层,表明SORLA参与神经元连接。总之,这些数据表明SORLA在突触发生中具有新作用。受体功能障碍可能与与眼部疾病有关的视网膜内层形成的形态和功能受损有关。

更新日期:2020-06-26
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