PMID- 36768481
OWN - NLM
STAT- MEDLINE
DCOM- 20230214
LR  - 20230214
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 3
DP  - 2023 Jan 21
TI  - Understanding the Role of ATP Release through Connexins Hemichannels during 
      Neurulation.
LID - 10.3390/ijms24032159 [doi]
LID - 2159
AB  - 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.
FAU - Tovar, Lina Mariana
AU  - Tovar LM
AD  - Laboratory of Physiology and Pharmacology for Neural Development, LAND, 
      Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
FAU - Burgos, Carlos Felipe
AU  - Burgos CF
AUID- ORCID: 0000-0001-6738-8589
AD  - Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
FAU - Yevenes, Gonzalo E
AU  - Yevenes GE
AD  - Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
FAU - Moraga-Cid, Gustavo
AU  - Moraga-Cid G
AUID- ORCID: 0000-0002-0260-8744
AD  - Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
FAU - Fuentealba, Jorge
AU  - Fuentealba J
AD  - Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
FAU - Coddou, Claudio
AU  - Coddou C
AD  - Departamento de Ciencias Biomedicas, Facultad de Medicina, Universidad Catolica 
      del Norte, Coquimbo 1781421, Chile.
FAU - Bascunan-Godoy, Luisa
AU  - Bascunan-Godoy L
AD  - Departamento de Botanica, Facultad de Ciencias Naturales y Oceanograficas, 
      Universidad de Concepcion, Concepcion 4030000, Chile.
FAU - Catrupay, Claudio
AU  - Catrupay C
AUID- ORCID: 0000-0002-8475-7873
AD  - Laboratory of Physiology and Pharmacology for Neural Development, LAND, 
      Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
FAU - Torres, Angel
AU  - Torres A
AD  - Laboratory of Physiology and Pharmacology for Neural Development, LAND, 
      Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
FAU - Castro, Patricio A
AU  - Castro PA
AUID- ORCID: 0000-0002-8131-3265
AD  - Laboratory of Physiology and Pharmacology for Neural Development, LAND, 
      Departamento de Fisiologia, Facultad de Ciencias Biologicas, Universidad de 
      Concepcion, Concepcion 4030000, Chile.
LA  - eng
GR  - 11160562/FONDECYT/
GR  - 220.033.112-4/VRID-UdeC/
GR  - 1211095/Fondecyt/
GR  - 1211473/ANID Fondecyt Regular N degrees /
GR  - NCN19_038/Millennium Nucleus for the Study of Pain (MiNuSPain)/
PT  - Journal Article
DEP - 20230121
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Connexins)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Animals
MH  - *Connexins/metabolism
MH  - Neurulation
MH  - Gap Junctions/metabolism
MH  - Neural Tube/metabolism
MH  - *Neural Tube Defects/metabolism
MH  - Adenosine Triphosphate/metabolism
PMC - PMC9916920
OTO - NOTNLM
OT  - ATP
OT  - connexins hemichannels
OT  - neural tube defects
OT  - neurulation
OT  - purinergic signalling
COIS- The authors declare no conflict of interest.
EDAT- 2023/02/12 06:00
MHDA- 2023/02/15 06:00
PMCR- 2023/01/21
CRDT- 2023/02/11 01:20
PHST- 2022/11/08 00:00 [received]
PHST- 2022/12/30 00:00 [revised]
PHST- 2023/01/04 00:00 [accepted]
PHST- 2023/02/11 01:20 [entrez]
PHST- 2023/02/12 06:00 [pubmed]
PHST- 2023/02/15 06:00 [medline]
PHST- 2023/01/21 00:00 [pmc-release]
AID - ijms24032159 [pii]
AID - ijms-24-02159 [pii]
AID - 10.3390/ijms24032159 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 21;24(3):2159. doi: 10.3390/ijms24032159.