GPR143 Membrane Protein Introduction

Introduction of GPR143

Encoded by gene GPR143, GPR143 was originally identified as the protein ocular albinism 1 (OA1), which belongs to G protein-coupled receptor (GPCR). Participation in various neurological processes made GPCR have numerous possibilities for therapeutic applications. GPR143 is targeted to melanosomes in pigment cells. The gene GPR143 consists of 9 exons and is translated into a seven transmembrane protein constituted with α-helix. The third α-helix is considered as the G protein binding domain.

Function of GPR143 Membrane Protein

GPR143 is mainly expressed in the retinal pigment epithelium and melanocytes with high levels, and it is considered to be involved in intracellular signal transduction mechanisms. GPR143 mutation/defection may cause ocular albinism type 1, also referred to as Nettleship-Falls type ocular albinism, an X-linked visual disorder characterized by the albinism associated with retinal abnormalities. GPR143 was evaluated to bind tyrosine and L-3,4-Dihydroxyphenylalanine (L-DOPA), a traditional therapeutic drug for Parkinson’s disease, to play a role in melanosome biogenesis, organization, and transport. The binding can stimulate Ca²⁺ influx into the cytoplasm, then enhances secretion of the neurotrophic factor SERPINF1 and relocalizes β-arrestin at the plasma membrane. The signaling transduction relies on a G_q-mediated pathway in melanocytic cells. The binding between GPR143 and L-DOPA in the nucleus tractus solitarii can mediate depressor and bradycardic responses. In addition, GPR143 contributes to the pathogenesis of age-related macular degeneration (AMD). So GPR143 could be developed into a drug target to prevent the Parkinson’s disease, ocular albinism type 1 and AMD.

Fig.1 Model of GPR143. (Pan, 2016)

Application of GPR143 Membrane Protein in Literature

1. Ueda S., et al. l-3, 4-Dihydroxyphenylalanine induces ptosis through a GPR143-independent mechanism in mice. Journal of pharmacological sciences. 2016, 132(1): 109-112. PubMed ID: 27622543
   
   

   The authors reveal that GPR143 is a candidate receptor for L-3,4-dihydroxyphenylalanine (L-DOPA), which can replenish the depleted brain dopamine in the patients of Parkinson's disease. L-DOPA induces ptosis in a GPR143-independent fashion in mice

2. Hiroshima Y., et al. The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii. British journal of pharmacology. 2014, 171(2): 403-414. PubMed ID: 29492402
   
   

   This article firstly demonstrates that GPR143 acted as a functional receptor for DOPA to mediate physiological and/or pharmacological responses in the CNS. It mediates the responses of depressor and bradycardic in the nucleus tractus solitarii.

3. Yan N., et al. A novel nonsense mutation of the GPR143 gene identified in a Chinese pedigree with ocular albinism. PloS one. 2012, 7(8): e43177. PubMed ID: 22916221
   
   

   Through the experiment of complete ophthalmologic examinations, including 4 patients, 7 carriers and 17 unaffected individuals in five-generation family, the authors report that the mutation p.Y269X (a substitution of tyrosine for adenine) of GPR143 is responsible for the pathogenesis of familial ocular albinism for the first time.

4. Masukawa D., et al. Localization of ocular albinism-1 gene product GPR143 in the rat central nervous system. Neuroscience research. 2014, 88: 49-57. PubMed ID: 25108060
   
   

   This article shows the unique distribution pattern of GPR143-immunoreactive neurons and/or cells in the rat CNS. The distribution area includes the hippocampus, cerebral cortex, cerebellum cortex, striatum, substantia nigra, hypothalamic median eminence and supraoptic nucleus, nucleus tractus solitarii and caudal ventrolateral medulla and rostral ventrolateral medulla, medial habenular nucleus and olfactory bulb.

5. McKay B.S. and Schwartz S.G. Pigmentation and macular degeneration: Is there a role for GPR143? J Ocul Pharmacol Ther. 2016, 32(1):3-4 PubMed ID: 26741053
   
   

   This article verifies the hypothesis that patients taking L-DOPA for movement disorders are protective against AMD due to GPR143-mediated elevation in retinal PEDF.

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