PUBLICATION
Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish
- Authors
- Zhang, J., Jing, M., Li, P., Sun, L., Pi, X., Jiang, N., Zhu, K.K., Li, H., Li, J., Wang, M., Zhang, J., Liu, M., Mu, H., Hu, Y., Cui, X.
- ID
- ZDB-PUB-230123-3
- Date
- 2023
- Source
- Biochimica et biophysica acta. Molecular basis of disease 1869(4): 166645 (Journal)
- Registered Authors
- Cui, Xiukun, Hu, Yanzhong
- Keywords
- Apoptosis, Cone degeneration, Cytoplasmic dynein 1, DLIC1, Rab8, Zebrafish
- MeSH Terms
-
- Animals
- Cone Opsins*/metabolism
- Cytoplasmic Dyneins/metabolism
- Dyneins/genetics
- Dyneins/metabolism
- Retinal Cone Photoreceptor Cells*/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 36682603 Full text @ BBA Molecular Basis of Disease
Citation
Zhang, J., Jing, M., Li, P., Sun, L., Pi, X., Jiang, N., Zhu, K.K., Li, H., Li, J., Wang, M., Zhang, J., Liu, M., Mu, H., Hu, Y., Cui, X. (2023) Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish. Biochimica et biophysica acta. Molecular basis of disease. 1869(4):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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping