Gpr143, also known as the gene product of ocular albinism 1 (OA1), is a G protein-coupled receptor. It is involved in multiple biological processes. In the context of exosome biogenesis, it controls the ESCRT-dependent pathway, interacting with HRS (an ESCRT-0 Subunit) to enable selective protein sorting into intraluminal vesicles [1]. It also plays a role in pigmentation-related pathways, which are associated with retinal-related functions and diseases [2,3].

Gain-and loss-of-function studies in mice demonstrated that Gpr143 promotes cancer metastasis by secreting exosomes and increasing cancer cell motility/invasion through the integrin/FAK/Src pathway [1]. In addition, Gpr143 mutations in humans are associated with ocular albinism type 1 (OA1), an X-linked infantile nystagmus syndrome, presenting with reduced vision, nystagmus, and iris and fundus hypopigmentation [4,5].

In conclusion, Gpr143 is crucial in exosome-mediated cancer metastasis and is closely related to retinal-associated diseases such as OA1. Mouse models have been instrumental in revealing its role in cancer metastasis, while human genetic studies of Gpr143 mutations have provided insights into the pathogenesis of ocular albinism and related nystagmus syndromes.

References:

1. Lee, Yu Jin, Shin, Kyeong Jin, Jang, Hyun-Jun, Suh, Pann-Ghill, Chae, Young Chan. 2023. GPR143 controls ESCRT-dependent exosome biogenesis and promotes cancer metastasis. In Developmental cell, 58, 320-334.e8. doi:10.1016/j.devcel.2023.01.006. https://pubmed.ncbi.nlm.nih.gov/36800996/

2. Figueroa, Anna G, McKay, Brian S. . GPR143 Signaling and Retinal Degeneration. In Advances in experimental medicine and biology, 1185, 15-19. doi:10.1007/978-3-030-27378-1_3. https://pubmed.ncbi.nlm.nih.gov/31884582/

3. McKay, Brian S. 2018. Pigmentation and vision: Is GPR143 in control? In Journal of neuroscience research, 97, 77-87. doi:10.1002/jnr.24246. https://pubmed.ncbi.nlm.nih.gov/29761529/

4. Xu, Jingling, Zheng, Yihan, Cheng, Lulu, Gu, Feng, Song, E. 2023. GPR143 mutations in an X-linked infantile nystagmus syndrome cohort in Southeast China. In Molecular vision, 29, 234-244. doi:. https://pubmed.ncbi.nlm.nih.gov/38222445/

5. Zhong, Junwei, You, Bing, Xu, Ke, Xie, Yue, Li, Yang. 2021. GPR143 genotypic and ocular phenotypic characterisation in a Chinese cohort with ocular albinism. In Ophthalmic genetics, 42, 717-724. doi:10.1080/13816810.2021.1958352. https://pubmed.ncbi.nlm.nih.gov/34346269/