Neurexin Regulates Visual Function via Mediating Retinoid Transport to Promote Rhodopsin Maturation

Neurexin Regulates Visual Function via Mediating Retinoid Transport to Promote Rhodopsin Maturation
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Neurexin 通过介导类视黄醇运输来促进视紫红质成熟来调节视觉功能

DOI:
10.1016/j.neuron.2012.11.012
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发表时间:
2013-01
期刊:
影响因子:
16.2
通讯作者:
Wei Xie
Wei Xie
中科院分区:
医学1区
文献类型:
--
作者:
Yao Tian;Tao Li;Mingkuan Sun;Didi Wan;Qian Li;Peipei Li;Zi Chao Zhang;Junhai Han;Wei Xie

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Neurexins是参与突触形成和突触调节的细胞黏附分子。尿素酶基因的突变与许多神经发育障碍有关,如自闭症。在这里,我们证明了果蝇α-Neuresin的同源物对果蝇的视觉功能至关重要。由于视紫红质水平降低,缺乏神经红素会导致视觉功能严重受损。我们发现,生色团水平的降低导致视紫红质成熟的缺陷,并且视黄素的运输需要神经红素。通过酵母双杂交筛选,我们发现neuresin与载脂蛋白I(APOL I)相互作用,APOL I是维甲酸和脂肪酸结合糖蛋白(RFABG)裂解产生的产物,在维甲酸转运中起作用。最后,我们证明了纽瑞新对载脂蛋白水平是必不可少的。我们的结果揭示了纽瑞辛在调节视黄醇转运和随后的视紫红质成熟中的作用,并提示纽瑞辛调节脂蛋白功能。
Neurexins are cell adhesion molecules involved in synapse formation and synaptic regulation. Mutations in theneurexingenes are linked to a number of neurodevelopmental disorders such as autism. Here, we show that theDrosophilahomolog of α-Neurexin is critical for fly visual function. Lack of Neurexin leads to significantly impaired visual function due to reduced rhodopsin levels. We show that the decreased chromophore levels cause deficits in rhodopsin maturation and that Neurexin is required for retinoid transport. Using yeast two-hybrid screening, we identify that Neurexin interacts with apolipoprotein I (ApoL I), a product generated by cleavage of retinoid- and fatty acid-binding glycoprotein (RFABG) that functions in retinoid transport. Finally, we demonstrate that Neurexin is essential for the apolipoproteins level. Our results reveal a role for Neurexin in mediating retinoid transport and subsequent rhodopsin maturation and suggest that Neurexin regulates lipoprotein function.
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