PANX3 Membrane Protein Introduction

Introduction of PANX3

Pannexin 3 (PANX3), encoded by the PANX3 gene in humans, is a member of pannexin family. Similar to the other two members of the pannexin family (PANX1 and PANX2), PANX3 also contains 4 transmembrane domains and cytoplasmic N and C termini. But, unlike PANX1 and PANX2 with the highest levels of expression in the central nervous system, PANX3 is predominantly expressed in skin, bone and cartilage tissue but absent from the nervous system. PANX3 is induced in the transient stage from the proliferation and differentiation of chondrocytes and osteoprogenitor cells. PANX3 gene is mapped to chromosome 11q24.2.

Function of PANX3 Membrane Protein

PANX3 is also known to be the structural component of gap junctions, which are consists of the connexin (Cx) and pannexin (Panx) protein families, and play a crucial role in cellular communication by mediating the transfer of ions (K⁺ and Ca²⁺), second messengers (cAMP, ATP, and inositol 1,4,5-trisphosphate), and other metabolites (glucose) as specialized transmembrane channels. In skeletal formation, PANX3 is demonstrated to regulate both chondrocyte and osteoblast differentiation via the activation of intracellular Ca²⁺ signaling pathways. Moreover, PANX3 ATP hemi-channel can switch the cell fate of chondrocytes and osteoblasts from proliferation to differentiation by regulating intracellular ATP/cAMP levels. Besides, it is also revealed that PANX3 inhibits osteoprogenitor cell proliferation and promotes cell cycle exit through the inactivation of Wnt/β-catenin signaling and the activation of p21. Altogether, PANX3 is essential for normal skeletal development and holds the potential for new therapies in the treatment of associated diseases and pathologies, such as osteoarthritis (OA).

Fig.1 Functions and its signaling pathways of Panx3 in osteoblast differentiation. (Ishikawa, 2017)

Application of PANX3 Membrane Protein in Literature

1. Pham T.L., et al. Expression of Pannexin 1 and Pannexin 3 during skeletal muscle development, regeneration, and Duchenne muscular dystrophy. J Cell Physiol. 2018, 233: 7057-7070. PubMed ID: 29744875
   
   

   In this article, the authors demonstrate that Panx1 and Panx3 are differentially expressed amongst skeletal muscle types with their levels being highly modulated during skeletal muscle development, regeneration, and dystrophy.

2. Song F., et al. The Role of Pannexin3-Modified Human Dental Pulp-Derived Mesenchymal Stromal Cells in Repairing Rat Cranial Critical-Sized Bone Defects. Cell Physiol Biochem. 2017, 44: 2174-2188. PubMed ID: 29241211
   
   

   This article indicates that Panx3 is a crucial modulator of human dental pulp-derived mesenchymal stromal cells (hDPSCs) differentiation by interacting with the Wnt/β-catenin signaling pathway.

3. Halliwill K.D., et al. Panx3 links body mass index and tumorigenesis in a genetically heterogeneous mouse model of carcinogen-induced cancer. Genome Med. 2016, 8: 83. PubMed ID: 27506198
   
   

   This article identifies several genetic loci that influence both body mass index (BMI) and carcinogenesis. It also reveals that Panx3 gene expression levels are associated with tumor susceptibility and inhibition of Panx3 function strongly influences inflammation, implicating Panx3 as a candidate gene that links these phenotypes through its effects on inflammation and lipid metabolism.

4. Bond S.R., et al. Pannexin 3 is required for late stage bone growth but not for initiation of ossification in avian embryos. Dev Dyn. 2016, 245: 913-924. PubMed ID: 27295565
   
   

   This article suggests that PANX3 hemi-channels is required to facilitate the transition of hypertrophic chondrocytes to osteoblasts, thereby achieving final bone size by the use of RCAS retroviral system to over-express and knockdown expression during endochondral bone formation.

5. Caskenette D., et al. Global deletion of Panx3 produces multiple phenotypic effects in mouse humeri and femora. J Anat. 2016, 228: 746-756. PubMed ID: 26749194
   
   

   This report indicates that Panx3 ablation produces the phenotypic effect in mouse femora and humeri, supporting that Panx3 has a role in regulating long bone growth and development.

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Reference

1. Ishikawa M and Yamada Y. (2017). The Role of Pannexin 3 in Bone Biology. J Dent Res. 96: 372-379.

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