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dc.contributor.author
Lafon Hughes, Laura I.
dc.contributor.author
Romeo Cardeillac, Carlos J.
dc.contributor.author
Cal Castillo, Karina B.
dc.contributor.author
Vilchez Larrea, Salomé Catalina
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dc.contributor.author
Sotelo Sosa, José R.
dc.contributor.author
Folle Ungo, Gustavo A.
dc.contributor.author
Fernandez Villamil, Silvia Hebe
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dc.contributor.author
Kun González, Alejandra E.
dc.date.available
2018-04-04T17:44:48Z
dc.date.issued
2017-05
dc.identifier.citation
Lafon Hughes, Laura I.; Romeo Cardeillac, Carlos J.; Cal Castillo, Karina B.; Vilchez Larrea, Salomé Catalina; Sotelo Sosa, José R.; et al.; Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model; PeerJ; PeerJ; 5; 5-2017; 1-24; e3318
dc.identifier.issn
2167-8359
dc.identifier.uri
http://hdl.handle.net/11336/40743
dc.description.abstract
Background: Poly-ADP-ribose (PAR) is a polymer synthesized by poly-ADP-ribose polymerases (PARPs) as a postranslational protein modification and catabolized mainly by poly-ADP-ribose glycohydrolase (PARG). In spite of the existence of cytoplasmic PARPs and PARG, research has been focused on nuclear PARPs and PAR, demonstrating roles in the maintenance of chromatin architecture and the participation in DNA damage responses and transcriptional regulation. We have recently detected non-nuclear PAR structurally and functionally associated to the E-cadherin rich zonula adherens and the actin cytoskeleton of VERO epithelial cells. Myelinating Schwann cells (SC) are stabilized by E-cadherin rich autotypic adherens junctions (AJ). We wondered whether PAR would map to these regions. Besides, we have demonstrated an altered microfilament pattern in peripheral nerves of Trembler-J (Tr-J) model of CMT1-E. We hypothesized that cytoplasmic PAR would accompany such modified F-actin pattern.
Methods: Wild-type (WT) and Tr-J mice sciatic nerves cryosections were subjected to immunohistofluorescence with anti-PAR antibodies (including antibody validation), F-actin detection with a phalloidin probe and DAPI/DNA counterstaining. Confocal image stacks were subjected to a colocalization highlighter and to semi-quantitative image analysis.
Results: We have shown for the first time the presence of PAR in sciatic nerves. Cytoplasmic PAR colocalized with F-actin at non-compact myelin regions in WT nerves. Moreover, in Tr-J, cytoplasmic PAR was augmented in close correlation with actin. In addition, nuclear PAR was detected in WT SC and was moderately increased in Tr-J SC.
Discussion: The presence of PAR associated to non-compact myelin regions (which constitute E-cadherin rich autotypic AJ/actin anchorage regions) and the co-alterations experienced by PAR and the actin cytoskeleton in epithelium and nerves, suggest that PAR may be a constitutive component of AJ/actin anchorage regions. Is PAR stabilizing the AJ-actin complexes? This question has strong implications in structural cell biology and cell signaling networks. Moreover, if PAR played a stabilizing role, such stabilization could participate in the physiological control of axonal branching. PARP and PAR alterations exist in several neurodegenerative pathologies including Alzheimer’s, Parkinson’s and Hungtington’s diseases. Conversely, PARP inhibition decreases PAR and promotes neurite outgrowth in cortical neurons in vitro. Coherently, the PARP inhibitor XAV939 improves myelination in vitro, ex vivo and in vivo. Until now such results have been interpreted in terms of nuclear PARP activity. Our results indicate for the first time the presence of PARylation in peripheral nerve fibers, in a healthy environment. Besides, we have evidenced a PARylation increase in Tr-J, suggesting that the involvement of cytoplasmic PARPs and PARylation in normal and neurodegenerative conditions should be re-evaluated.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
PeerJ
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Poly(Adp-Ribosylation)
dc.subject
Actin Cytoskeleton
dc.subject
Trembler-J
dc.subject
Neurodegeneration
dc.subject.classification
Otras Ciencias Biológicas
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-04-04T14:16:35Z
dc.journal.volume
5
dc.journal.pagination
1-24; e3318
dc.journal.pais
Estados Unidos
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dc.description.fil
Fil: Lafon Hughes, Laura I.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Romeo Cardeillac, Carlos J.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Cal Castillo, Karina B.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Vilchez Larrea, Salomé Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Sotelo Sosa, José R.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Folle Ungo, Gustavo A.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay
dc.description.fil
Fil: Fernandez Villamil, Silvia Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
dc.description.fil
Fil: Kun González, Alejandra E.. Instituto de Investigaciones Biológicas "Clemente Estable"; Uruguay. Universidad de la República; Uruguay
dc.journal.title
PeerJ
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://peerj.com/articles/3318
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://doi.org/10.7717/peerj.3318
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