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Int J Mol Sci 2023 Jan 21;243:. doi: 10.3390/ijms24032159.
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Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation.

Tovar LM , Burgos CF , Yévenes GE , Moraga-Cid G , Fuentealba J , Coddou C , Bascunan-Godoy L , Catrupay C , Torres A , Castro PA .

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis. Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.

PubMed ID: 36768481
PMC ID: PMC9916920
Article link: Int J Mol Sci

Species referenced: Xenopus laevis
Genes referenced: fgf2 gja1 gja10 gja3 gja4 gja4.2 gja9 gjb1 gjb2 gjb3 gjb5 gjb7 gjc1 gjc2 gjd4 sub1
GO keywords: neural plate development [+]

Phenotypes: Xla Wt + carbenoxolone (Fig. 2 B) [+]

Article Images: [+] show captions
References [+] :
Abbracchio, Purinergic signalling in the nervous system: an overview. 2009, Pubmed