Dync1li1, also known as Dynein cytoplasmic 1 light intermediate chain 1 (LIC1), is a core subunit of the dynein motor complex. It interacts with various cargo adaptors to regulate Rab-mediated endosomal recycling and lysosomal degradation, playing a crucial role in intracellular retrograde transport [2,3]. This gene is essential for many biological processes as it affects dynein motor function, Rab binding capabilities, and cytoplasmic cargo trafficking. Genetic models, such as knockout mice, have been valuable in studying its functions [1].

In mice, deletion of Dync1li1 leads to early-onset progressive loss of cochlear hair cells (HCs) via apoptosis and subsequent hearing loss. It destabilizes dynein, alters its normal function, results in a thinner Golgi apparatus and accumulates LC3 + autophagic vacuoles, triggering HC apoptosis. Knocking down Dync1li1 in OC1 cells impairs the transportation of autophagosomes to lysosomes, causing autophagosome accumulation and HC apoptosis [1]. In zebrafish, dync1li1 mutants display increased angiogenesis, and LIC1-deficient human endothelial cells show increased cell surface levels of VEGFR2, SRC phosphorylation, and Rab11-mediated endosomal recycling. Also, knockout of Dync1li1 in zebrafish leads to progressive degeneration of retinal cone photoreceptors, especially blue cones, due to disturbed Rab8 transport [2,3,4].

In conclusion, Dync1li1 is crucial for the survival of cochlear hair cells by regulating autophagosome transportation, and for restricting angiogenesis and maintaining the function and survival of cone photoreceptors. The gene knockout models in mice and zebrafish have significantly contributed to understanding its roles in hearing loss, angiogenesis-related diseases, and retinal cone-related disorders [1,2,3,4].

References:

1. Zhang, Yuan, Zhang, Shasha, Zhou, Han, Gao, Xia, Chai, Renjie. 2022. Dync1li1 is required for the survival of mammalian cochlear hair cells by regulating the transportation of autophagosomes. In PLoS genetics, 18, e1010232. doi:10.1371/journal.pgen.1010232. https://pubmed.ncbi.nlm.nih.gov/35727824/

2. Johnson, Dymonn, Colijn, Sarah, Richee, Jahmiera, Weinstein, Brant M, Stratman, Amber N. 2024. Angiogenesis is limited by LIC1-mediated lysosomal trafficking. In Angiogenesis, 27, 943-962. doi:10.1007/s10456-024-09951-7. https://pubmed.ncbi.nlm.nih.gov/39356418/

3. Johnson, Dymonn, Colijn, Sarah, Richee, Jahmiera, Weinstein, Brant M, Stratman, Amber N. 2024. Regulation of angiogenesis by endocytic trafficking mediated by cytoplasmic dynein 1 light intermediate chain 1. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.04.01.587559. https://pubmed.ncbi.nlm.nih.gov/38903077/

4. Zhang, Jing, Jing, Min, Li, Ping, Hu, Yanzhong, Cui, Xiukun. 2023. Knockout of DLIC1 leads to retinal cone degeneration via disturbing Rab8 transport in zebrafish. In Biochimica et biophysica acta. Molecular basis of disease, 1869, 166645. doi:10.1016/j.bbadis.2023.166645. https://pubmed.ncbi.nlm.nih.gov/36682603/