Ptprg-KO Mouse

Ptprg, or Protein Tyrosine Phosphatase Receptor Type G, is a gene that interacts with and regulates several tyrosine kinases, exerting a tumor suppressor role in several types of cancers [2]. It contains a carbonic anhydrase-like domain and a fibronectin type III domain which are associated with [HCO3-] sensing in vascular and renal tissues and cell adhesion respectively. The contactins family has been identified as possible interactors of PTPRG [2]. It is also potentially related to inflammatory processes and could serve as an inflammatory marker [2].

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

In summary, Ptprg has important functions in cancer and neurodegenerative diseases. In cancer, it acts as a tumor suppressor. In AD, Ptprg-mediated regulation of VIRMA and subsequent inhibition of mitophagy in neurons is a potential pathway through which microglia and neuronal Ptprg modify neuronal connections during disease progression. These findings from in vivo-like studies in mouse models of AD help us understand the role of Ptprg in disease-related biological processes and potentially guide the development of therapies for these conditions [1,2].

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/