Aplnr, also known as Apelin receptor, APJ or AGTRLl1, is a seven-transmembrane G protein-coupled receptor. The Apelin/APLNR system is involved in regulating numerous physiological and pathological processes, such as metabolism, angiogenesis, and cardiovascular function, and participates in immune response and immune regulation through pathways like PI3K-Akt and ERK-MAPK [1,3]. Apelin, an endogenous ligand of Aplnr, activates it and is key in cardiovascular homeostasis [2]. Genetic models, especially knockout mouse models, are valuable for studying Aplnr's functions.

In Aplnr knockout mice, there are sex-specific changes in conditioned fear, with male mice showing enhanced context-and cue-dependent fear responses, indicating Aplnr's role in the central nervous system [4]. In the hematopoietic system, deletion of Aplnr in mouse embryonic stem cells impairs the production of hematopoietic stem and progenitor cells, suggesting that APLNR signaling is required for their generation [6]. Mice deficient in Aplnr or its ligand apelin display dramatic alterations in muscle function with age, highlighting Aplnr's importance in muscle function [5].

In conclusion, Aplnr is crucial for multiple biological processes including those in the central nervous system, hematopoietic system, and muscle. The use of Aplnr knockout mouse models has provided insights into its role in diseases related to fear-related disorders, hematopoietic system abnormalities, and age-associated muscle weakness, offering potential therapeutic targets for these conditions.

References:

1. Yang, Yuqin, Chen, Meilin, Qiu, Yanbing, Huang, Yumei, Zhang, Wenling. 2022. The Apelin/APLNR system modulates tumor immune response by reshaping the tumor microenvironment. In Gene, 834, 146564. doi:10.1016/j.gene.2022.146564. https://pubmed.ncbi.nlm.nih.gov/35598689/

2. Wang, Wei-Wei, Ji, Su-Yu, Zhang, Wenjia, Zhang, Yan, Zhang, Yan. 2024. Structure-based design of non-hypertrophic apelin receptor modulator. In Cell, 187, 1460-1475.e20. doi:10.1016/j.cell.2024.02.004. https://pubmed.ncbi.nlm.nih.gov/38428423/

3. Liu, Yingying, Ma, Xiaochuan, Yang, Hui, Liu, Suling, Hu, Liaoyuan A. . APLNR Regulates IFN-γ signaling via β-arrestin 1 mediated JAK-STAT1 pathway in melanoma cells. In The Biochemical journal, 479, 385-399. doi:10.1042/BCJ20210813. https://pubmed.ncbi.nlm.nih.gov/35084016/

4. Laudermilk, Lucas T, Harper, Kathryn M, Moy, Sheryl S, Koller, Beverly, Maitra, Rangan. 2020. Aplnr knockout mice display sex-specific changes in conditioned fear. In Behavioural brain research, 400, 113059. doi:10.1016/j.bbr.2020.113059. https://pubmed.ncbi.nlm.nih.gov/33309737/

5. Vinel, Claire, Lukjanenko, Laura, Batut, Aurelie, Valet, Philippe, Dray, Cedric. 2018. The exerkine apelin reverses age-associated sarcopenia. In Nature medicine, 24, 1360-1371. doi:10.1038/s41591-018-0131-6. https://pubmed.ncbi.nlm.nih.gov/30061698/

6. Jackson, Melany, Fidanza, Antonella, Taylor, A Helen, Medvinsky, Alexander, Forrester, Lesley M. 2021. Modulation of APLNR Signaling Is Required during the Development and Maintenance of the Hematopoietic System. In Stem cell reports, 16, 727-740. doi:10.1016/j.stemcr.2021.02.003. https://pubmed.ncbi.nlm.nih.gov/33667414/