PANX3

Official Full Name

pannexin 3

Organism

Homo sapiens

GeneID

116337

Background

The protein encoded by this gene belongs to the innexin family. Innexin family members are known to be the structural components of gap junctions. [provided by RefSeq, Jul 2008]

Synonyms

PX3;

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Detailed Information

Pannexin 3 channels in health and disease

The family of integral membrane is composited by Pannexin 1, 2, and 3 (PANX1, PANX2, PANX3), channel-forming glycoproteins were discovered from their homology to the invertebrate gap junction proteins innexins. Facilitation effect of PANX3 channels on the passage of signaling molecules such as ATP at the cell surface and Ca²⁺ intracellularly is influential in the cellular processes such as differentiation. So, there need some considerations of PANX3 being an additional channel that contributes to purinergic signalling.

Located on chromosome 9 in mice and 11 (11q24.2) in humans, where PANX3 gene consists of 4 exons and 3 introns and encoded protein share 93% conservation between the two species. 392 amino acids composited PANX3 with the molecular weight of ~43 kDa is ranked as the smallest member of the family, and it forms large-pore, single-membrane channels by oligomerization, but its stoichiometry is still unknown. Most PANX3 studies have been focused on its role in bone, teeth, and cartilage, but coverage of other areas such as skin, adipose, and vasculature also excited interests. However, the mechanisms of PANX3 function in tissue homeostasis and its dysregulation in disease are still not fully understood. Revelation of involvement of PANX3 in purinergic signalling in osteoblasts and monocytes may put forward the question of whether its interaction with any purinergic receptors is similar to PANX1 in the inflammasome or not? Therapeutic potential of PANX3 in bone and cartilage associated pathologies such as osteosarcoma, osteoarthritis, osteoporosis, and arthritis has been brought into the investigation in consideration of its role in chondrocyte and osteoblast differentiation. Moreover, its role in differentiation is broad or cell-type specific would be determined by investigation into PANX3 in cell specialization. Global PANX3 KO mouse models derived PANX3 findings is accompanied with compensation and contradictory evidence since the dependence on the model used. So, in the future, PANX3 action could be identified distinctly in healthy tissue and disease by cell-type specific and conditional PANX3 KO mouse models.

Role of PANX3 in age-associated and injury-induced intervertebral disc degeneration

Role of PANX3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture was investigated in PANX3 knockout mice, and loss of PANX3 was found to be capable of significantly impacting the progression of age-associated histopathological IVD degeneration, while it is also related with decreased gene expression of Acan, Col1a1, Mmp13 and Runx2 and altered localization of COLX in the IVD at 19 months-of-age. Association between clusters of hypertrophic cells in the AF and increased pericellular proteoglycan accumulation, disruptions in lamellar organization and increased lamellar thickness has also been revealed in the histological analysis of wild-type mice in subsequent from IVD injury in the caudal spine. Hypertrophic AF cells were rarely detected and AF structure was largely preserved post-injury in PANX3 knockout mice.

Figure 1. Panx3 regulates chondrogenesis and osteogenesis by promoting cell cycle exit and cell differentiation. (Ishikawa M, et al. 2016)

References:

Ishikawa M, Yamada Y. The role of pannexin 3 in bone biology. Journal of dental research, 2017, 96(4): 372-379.
O'Donnell B L, Penuela S. Pannexin 3 channels in health and disease. Purinergic Signalling, 2021, 17(4): 577-589.
Serjeant M, Moon P M, Quinonez D, et al. The role of Panx3 in age-associated and injury-induced intervertebral disc degeneration. International journal of molecular sciences, 2021, 22(3): 1080.

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