Panx1 Regulates Cellular Properties of Keratinocytes and Dermal Fibroblasts in Skin Development and Wound Healing

Peñuela, Silvia; Kelly, John J.; Churko, Jared M.; Barr, Kevin; Berger, Amy; Laird, Dale W.

doi:10.1038/jid.2014.86

Cited by 61 publications

(97 citation statements)

References 49 publications

(71 reference statements)

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“…Further, in P2X7 −/− mice the rate of wound repair was negatively affected. The absence of Panx1 at the wound edge is in line with another study about Panx1 in skin development and wound healing (Penuela et al, 2014a). …”

Section: Panx1 In the Cornea: Implications For Wound Healingsupporting

confidence: 90%

Emerging functions of pannexin 1 in the eye

Kurtenbach

Zoidl

2014

Front. Cell. Neurosci.

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Pannexin 1 (Panx1) is a high-conductance, voltage-gated channel protein found in vertebrates. Panx1 is widely expressed in many organs and tissues, including sensory systems. In the eye, Panx1 is expressed in major divisions including the retina, lens and cornea. Panx1 is found in different neuronal and non-neuronal cell types. The channel is mechanosensitive and responds to changes in extracellular ATP, intracellular calcium, pH, or ROS/nitric oxide. Since Panx1 channels operate at the crossroad of major signaling pathways, physiological functions in important autocrine and paracrine feedback signaling mechanisms were hypothesized. This review starts with describing in depth the initial Panx1 expression and localization studies fostering functional studies that uncovered distinct roles in processing visual information in subsets of neurons in the rodent and fish retina. Panx1 is expressed along the entire anatomical axis from optical nerve to retina and cornea in glia, epithelial and endothelial cells as well as in neurons. The expression and diverse localizations throughout the eye points towards versatile functions of Panx1 in neuronal and non-neuronal cells, implicating Panx1 in the crosstalk between immune and neural cells, pressure related pathological conditions like glaucoma, wound repair or neuronal cell death caused by ischemia. Summarizing the literature on Panx1 in the eye highlights the diversity of emerging Panx1 channel functions in health and disease.

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Section: Panx1 In the Cornea: Implications For Wound Healingsupporting

confidence: 90%

Emerging functions of pannexin 1 in the eye

Kurtenbach

Zoidl

2014

Front. Cell. Neurosci.

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“…However, the lack of overt phenotypes in global Panx1 KO mice may be due, at least in part, to compensation by other pannexins. For example, when Panx1 was constitutively deleted in a Panx1 KO mouse, there was an increase in Panx3 expression in dorsal skin (60). A similar upregulation of Panx3 expression was observed in the wall of thoracodorsal arteries of Panx1 KO mice compared with C57Bl/6 controls (61).…”

Section: Discussionmentioning

confidence: 52%

A Germline Variant in the PANX1 Gene Has Reduced Channel Function and Is Associated with Multisystem Dysfunction

Shao

Lindstrom

Shi

et al. 2016

Journal of Biological Chemistry

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Pannexin1 (PANX1) is probably best understood as an ATP release channel involved in paracrine signaling. Given its ubiquitous expression, PANX1 pathogenic variants would be expected to lead to disorders involving multiple organ systems. Using whole exome sequencing, we discovered the first patient with a homozygous PANX1 variant (c.650G3 A) resulting in an arginine to histidine substitution at position 217 (p.Arg217His). The 17-year-old female has intellectual disability, sensorineural hearing loss requiring bilateral cochlear implants, skeletal defects, including kyphoscoliosis, and primary ovarian failure. Her consanguineous parents are each heterozygous for this variant but are not affected by the multiorgan syndromes noted in the proband. Expression of the p.Arg217His mutant in HeLa, N2A, HEK293T, and Ad293 cells revealed normal PANX1 glycosylation and cell surface trafficking. Dye uptake, ATP release, and electrophysiological measurements revealed p.Arg217His to be a loss-of-function variant. Co-expression of the mutant with wild-type PANX1 suggested the mutant was not dominantnegative to PANX1 channel function. Collectively, we demonstrate a PANX1 missense change associated with human disease in the first report of a "PANX1-related disorder."Pannexins are a new class of large-pore channels that were discovered early in the new millennium (1, 2

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“…It is worth noting that expression of CALHM1, another channel with structural similarities to pannexins and ATP release capability (Siebert et al, 2013; Taruno et al, 2013) was not detected in the OE (unpublished data). Finally, compensatory regulation of connexins or pannexin proteins (Lohman and Isakson, 2014; Penuela et al, 2014) needs to be investigated to clarify synergistic or competing mechanisms of ATP efflux without Panx1 channels.…”

Section: Discussionmentioning

confidence: 99%

Investigation of olfactory function in a Panx1 knock out mouse model

Kurtenbach

Whyte-Fagundes

Gelis

et al. 2014

Front. Cell. Neurosci.

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Pannexin 1 (Panx1), the most extensively investigated member of a channel-forming protein family, is able to form pores conducting molecules up to 1.5 kDa, like ATP, upon activation. In the olfactory epithelium (OE), ATP modulates olfactory responsiveness and plays a role in proliferation and differentiation of olfactory sensory neurons (OSNs). This process continuously takes place in the OE, as neurons are replaced throughout the whole lifespan. The recent discovery of Panx1 expression in the OE raises the question whether Panx1 mediates ATP release responsible for modulating chemosensory function. In this study, we analyzed pannexin expression in the OE and a possible role of Panx1 in olfactory function using a Panx1−/− mouse line with a global ablation of Panx1. This mouse model has been previously used to investigate Panx1 functions in the retina and adult hippocampus. Here, qPCR, in-situ hybridization, and immunohistochemistry (IHC) demonstrated that Panx1 is expressed in axon bundles deriving from sensory neurons of the OE. The localization, distribution, and expression of major olfactory signal transduction proteins were not significantly altered in Panx1−/− mice. Further, functional analysis of Panx1−/− animals does not reveal any major impairment in odor perception, indicated by electroolfactogram (EOG) measurements and behavioral testing. However, ATP release evoked by potassium gluconate application was reduced in Panx1−/− mice. This result is consistent with previous reports on ATP release in isolated erythrocytes and spinal or lumbar cord preparations from Panx1−/− mice, suggesting that Panx1 is one of several alternative pathways to release ATP in the olfactory system.

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Panx1 Regulates Cellular Properties of Keratinocytes and Dermal Fibroblasts in Skin Development and Wound Healing

Cited by 61 publications

References 49 publications

Emerging functions of pannexin 1 in the eye

Emerging functions of pannexin 1 in the eye

A Germline Variant in the PANX1 Gene Has Reduced Channel Function and Is Associated with Multisystem Dysfunction

Investigation of olfactory function in a Panx1 knock out mouse model

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