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Pannexin 3 channels in health and disease

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Abstract

Pannexin 3 (PANX3) is a member of the pannexin family of single membrane channel-forming glycoproteins. Originally thought to have a limited localization in cartilage, bone, and skin, PANX3 has now been detected in a variety of other tissues including skeletal muscle, mammary glands, the male reproductive tract, the cochlea, blood vessels, small intestines, teeth, and the vomeronasal organ. In many cell types of the musculoskeletal system, such as osteoblasts, chondrocytes, and odontoblasts, PANX3 has been shown to regulate the balance of proliferation and differentiation. PANX3 can be induced during progenitor cell differentiation, functioning at the cell surface as a conduit for ATP and/or in the endoplasmic reticulum as a calcium leak channel. Evidence in osteoblasts and monocytes also highlight a role for PANX3 in purinergic signalling through its function as an ATP release channel. PANX3 is critical in the development and ageing of bone and cartilage, with its levels temporally regulated in other tissues such as skeletal muscle, skin, and the cochlea. In diseases such as osteoarthritis and intervertebral disc degeneration, PANX3 can have either protective or detrimental roles depending on if the disease is age-related or injury-induced. This review will discuss PANX3 function in tissue growth and regeneration, its role in cellular differentiation, and how it becomes dysregulated in disease conditions such as obesity, Duchenne’s muscular dystrophy, osteosarcoma, and non-melanoma skin cancer, where most of the findings on PANX3 function can be attributed to the characterization of Panx3 KO mouse models.

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Funding

Western University and Petro-Canada Young Innovator award to SP.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada

    Brooke L. O’Donnell & Silvia Penuela

  2. Department of Oncology, Division of Experimental Oncology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada

    Silvia Penuela

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  1. Brooke L. O’Donnell
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  2. Silvia Penuela
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Correspondence to Silvia Penuela.

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Experiments performed on animals were approved by the Animal Care Committee of the University Council on Animal Care at the University of Western Ontario, London ON, Canada (UWO # 2019–069), and in accordance with relevant guidelines and regulations.

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This article is part of the Topical Collection on The contribution of pannexin-1, connexins and CALHM ATP-release channels to purinergic signalling

Guest Editor: Charles Kennedy

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O’Donnell, B.L., Penuela, S. Pannexin 3 channels in health and disease. Purinergic Signalling 17, 577–589 (2021). https://doi.org/10.1007/s11302-021-09805-7

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