Ptprg, or Protein Tyrosine Phosphatase Receptor Type G, is known to interact with and regulate several tyrosine kinases. It contains a carbonic anhydrase-like domain (CAH) and a fibronectin type III domain in the N-terminal portion, which are associated with its role as a [HCO3-] sensor in vascular and renal tissues and a possible interaction domain for cell adhesion respectively. It has been implicated in various biological processes and diseases, with its ligands including the contactins family (CNTN) [2].

In Alzheimer's disease (AD), single-cell and spatial transcriptomics studies found that a microglia subpopulation Mic_PTPRG can communicate with specific neurons, causing them to express PTPRG. In neurons, PTPRG binds and upregulates the m6A methyltransferase VIRMA, inhibiting the translation of PRKN mRNA and suppressing mitophagy. As the disease progresses, this leads to the reprogramming of energy and nutrient metabolic pathways in neurons, ultimately resulting in their death [1].

In summary, Ptprg plays a role in cell signaling regulation, potentially acting as an [HCO3-] sensor and cell adhesion mediator. In AD, its interaction with VIRMA in neurons affects mitophagy and neuronal survival. These findings from model-based research, such as the studies in AD mouse models, enhance our understanding of Ptprg's functions in normal and disease-related biological processes.

References:

1. Zou, Donghua, Huang, Xiaohua, Lan, Yating, Mao, Yingwei, Luo, Jiefeng. 2024. Single-cell and spatial transcriptomics reveals that PTPRG activates the m6A methyltransferase VIRMA to block mitophagy-mediated neuronal death in Alzheimer's disease. In Pharmacological research, 201, 107098. doi:10.1016/j.phrs.2024.107098. https://pubmed.ncbi.nlm.nih.gov/38325728/

2. Boni, Christian, Laudanna, Carlo, Sorio, Claudio. 2022. A Comprehensive Review of Receptor-Type Tyrosine-Protein Phosphatase Gamma (PTPRG) Role in Health and Non-Neoplastic Disease. In Biomolecules, 12, . doi:10.3390/biom12010084. https://pubmed.ncbi.nlm.nih.gov/35053232/