Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish
Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish
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敲除 DLIC1 通过干扰斑马鱼 Rab8 运输导致视网膜锥体变性
DOI：
10.1016/j.bbadis.2023.166645
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Xiukun Cui
中科院分区：
文献类型：
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作者：
Jing Zhang;Min Jing;Ping Li;Luqian Sun;Xiahui Pi;Ning Jiang;Ke-ke Zhu;Hui Li;Jing Li;Mingli Wang;Jun Zhang;Mugen Liu;Hongmei Mu;Yanzhong Hu;Xiukun Cui
视网膜感光器执行光转导功能，并需要一个有效的系统将材料（例如蛋白质和脂质）从内节运输到外节。细胞质动力蛋白 1 是负端定向的微管马达，参与细胞质中的货物运输。然而，动力蛋白 1 马达在光感受器货物运输和视网膜发育中的作用仍然不明确。在我们目前的研究中，使用 CRISPR-Cas9 技术在斑马鱼中消除了轻中间链蛋白 DLIC1（由 dync1li1 编码），该蛋白连接激活适配器以结合动力蛋白 1 马达中的多种货物。 dync1li1−/−斑马鱼表现出视网膜锥体光感受器（尤其是蓝色锥体）的进行性退化。 dync1li1−/−斑马鱼的视网膜杆不受影响。 DLIC1 的敲除导致 dync1li1−/− 视网膜中视锥细胞视蛋白的异常表达和定位。 TUNEL 染色表明，dync1li1−/− 斑马鱼光感受器中视锥蛋白异常积累后诱导细胞凋亡。 Rab8 传输在 dync1li1−/− 视网膜中受到干扰，而不是 Rab11 传输。我们的数据表明，DLIC1 是视锥光感受器功能维持和存活所必需的，并暗示细胞质动力蛋白 1 马达在光感受器货物运输中的重要作用。
Retinal photoreceptors execute phototransduction functions and require an efficient system for the transport of materials (e.g.proteins and lipids) from inner segments to outer segments. Cytoplasmic dynein 1 is a minus-end-directed microtubule motor and participates in cargo transport in the cytoplasm. However, the roles of dynein 1 motor in photoreceptor cargo transport and retinal development are still ambiguous. In our present study, the light intermediate chain protein DLIC1 (encoded bydync1li1), links activating adaptors to bind diverse cargos in the dynein 1 motor, was depleted using CRISPR-Cas9 technology in zebrafish. Thedync1li1−/−zebrafish displayed progressive degeneration of retinal cone photoreceptors, especially blue cones. The retinal rods were not affected indync1li1−/−zebrafish. Knockout of DLIC1 resulted in abnormal expression and localization of cone opsins indync1li1−/−retinas. TUNEL staining suggested that apoptosis was induced after aberrant accumulation of cone opsins in photoreceptors ofdync1li1−/−zebrafish. Instead of Rab11 transport, Rab8 transport was disturbed indync1li1−/−retinas. Our data demonstrate that DLIC1 is required for function maintenance and survival of cone photoreceptors, and hint at an essential role of the cytoplasmic dynein 1 motor in photoreceptor cargo transport.