Molecular studies into cell biological role of Copine-4 in Retinal Ganglion Cells.
Molecular studies into cell biological role of Copine-4 in Retinal Ganglion Cells.
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DOI：
10.1371/journal.pone.0255860
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Badea TC
中科院分区：
文献类型：
--
作者：
Goel M;Aponte AM;Wistow G;Badea TC
视网膜细胞类型形态多样性的分子机制知之甚少。我们以前曾报道，几个成员的Copine家族的钙依赖性膜衔接子表达在视网膜神经节细胞和转录调控Brn 3转录因子。几种Copines在视网膜中富集，它们的过度表达导致HEK 293细胞中的形态学变化-形成细长的突起-，使人联想到神经突。然而，Copines在视网膜中的作用在很大程度上是未知的。我们现在研究Cpne 4，其表达仅限于视网膜神经节细胞的Copine。Cpne 4在RGC中的过表达导致在树突上形成大的静脉曲张，但没有明显影响树突或轴突的形成。蛋白质相互作用的研究，使用酵母双杂交分析从整个视网膜cDNA揭示了两个Cpne 4相互作用的蛋白质-宿主细胞因子1和Morn 2。使用Cpne 4或其vonWillebrand A结构域拉下的视网膜裂解物的质谱分析显示207个相互作用蛋白。对发现的蛋白质的基因本体论分析表明，Cpne 4参与视网膜中的几种代谢和信号通路。
The molecular mechanisms underlying morphological diversity in retinal cell types are poorly understood. We have previously reported that several members of the Copine family of Ca-dependent membrane adaptors are expressed in Retinal Ganglion Cells and transcriptionally regulated by Brn3 transcription factors. Several Copines are enriched in the retina and their over-expression leads to morphological changes -formation of elongated processes-, reminiscent of neurites, in HEK293 cells. However, the role of Copines in the retina is largely unknown. We now investigate Cpne4, a Copine whose expression is restricted to Retinal Ganglion Cells. Over-expression of Cpne4 in RGCs in vivo led to formation of large varicosities on the dendrites but did not otherwise visibly affect dendrite or axon formation. Protein interactions studies using yeast two hybrid analysis from whole retina cDNA revealed two Cpne4 interacting proteins–Host Cell Factor 1 and Morn2. Mass Spectrometry analysis of retina lysate pulled down using Cpne4 or its vonWillebrand A domain showed 207 interacting proteins. A Gene Ontology analysis of the discovered proteins suggests that Cpne4 is involved in several metabolic and signaling pathways in the retina.
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