Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish

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

doi:10.1016/j.bbadis.2023.166645

Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish

Biochim Biophys Acta Mol Basis Dis. 2023 Apr;1869(4):166645. doi: 10.1016/j.bbadis.2023.166645. Epub 2023 Jan 20.

Authors

Jing Zhang¹, Min Jing¹, Ping Li¹, Luqian Sun¹, Xiahui Pi¹, Ning Jiang¹, Ke-Ke Zhu², Hui Li¹, Jing Li¹, Mingli Wang¹, Jun Zhang¹, Mugen Liu³, Hongmei Mu⁴, Yanzhong Hu⁵, Xiukun Cui⁶

Affiliations

¹ Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, China.
² Kaifeng Key Lab of Myopia and Cataract, Kaifeng Central Hospital, Kaifeng, China.
³ College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
⁴ Kaifeng Key Lab of Myopia and Cataract, Kaifeng Central Hospital, Kaifeng, China. Electronic address: muhongmeik@126.com.
⁵ Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, China; Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: hyz@henu.edu.cn.
⁶ Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital, School of Medicine, Henan University, Kaifeng, China. Electronic address: xkcui@henu.edu.cn.

PMID: 36682603
DOI: 10.1016/j.bbadis.2023.166645

Abstract

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 by dync1li1), links activating adaptors to bind diverse cargos in the dynein 1 motor, was depleted using CRISPR-Cas9 technology in zebrafish. The dync1li1^-/- zebrafish displayed progressive degeneration of retinal cone photoreceptors, especially blue cones. The retinal rods were not affected in dync1li1^-/- zebrafish. Knockout of DLIC1 resulted in abnormal expression and localization of cone opsins in dync1li1^-/- retinas. TUNEL staining suggested that apoptosis was induced after aberrant accumulation of cone opsins in photoreceptors of dync1li1^-/- zebrafish. Instead of Rab11 transport, Rab8 transport was disturbed in dync1li1^-/- 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.

Keywords: Apoptosis; Cone degeneration; Cytoplasmic dynein 1; DLIC1; Rab8; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cone Opsins* / metabolism
Cytoplasmic Dyneins* / genetics
Cytoplasmic Dyneins* / metabolism
Dyneins / genetics
Dyneins / metabolism
Retinal Cone Photoreceptor Cells* / metabolism
Zebrafish / genetics
Zebrafish / metabolism

Substances

Cone Opsins
Cytoplasmic Dyneins
Dyneins
Rab8a protein, zebrafish
dync1li1 protein, zebrafish

Supplementary concepts

Retinal Cone Dystrophy 1