Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy

Beppu, Minako; Sawai, Setsu; Satoh, Mamoru; Mori, Masahiro; Kazami, Takahiro; Misawa, Sonoko; Shibuya, Kazumoto; Ishibashi, Masayoshi; Sogawa, Kazuyuki; Kado, Satoshi; Kodera, Yasuhiro; Nomura, Fumio; Kuwabara, Satoshi

doi:10.1016/j.jneuroim.2015.07.012

Cited by 9 publications

(8 citation statements)

References 35 publications

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“…Tr-J mice sciatic nerve has marked alterations in junctional proteins including delocalized E-cadherin (Devaux & Scherer, 2005). In turn, cumulative evidence indicates that adherens junctions proteins (E-cadherin, catenins, vinculin), some of which can act as NACos, may play a significant role in the myelination process (Tricaud et al, 2005; Perrin-Tricaud, Rutishauser & Tricaud, 2007; Ye et al, 2009; Peng et al, 2010; Beppu et al, 2015; Basak et al, 2015). For example, E-cadherin enhances neuroregulin-1 (NRG1) signaling and promotes Schwann cell myelination (Basak et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

Lafon-Hughes

Cardeillac

Castillo

et al. 2017

PeerJ

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BackgroundPoly-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.MethodsWild-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.ResultsWe 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.DiscussionThe 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.

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Section: Discussionmentioning

confidence: 99%

Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

Lafon-Hughes

Cardeillac

Castillo

et al. 2017

PeerJ

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“…The active form of Vcn is localized to focal adhesions at membranes and participates in their regulation. (17) The recruitment of Vcn is important for the maintenance of the epithelial barrier, which is achieved by protecting endothelial junctions from opening during force-dependent remodeling. (11) Zemljic-Harpf and colleagues reported that Vcn de ciency contributes to cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

High serum VE-cadherin and vinculin concentrations are markers of the disruption of vascular integrity during acute aortic dissection

Wang

et al. 2021

Preprint

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Background In the present study, we measured the serum vascular endothelial cadherin (VEC) and vinculin (Vcn) concentrations in patients with acute aortic dissection (AAD) to evaluate their diagnostic value for this condition. Methods One hundred patients with AAD and 60 matched controls were included in the study. The serum concentrations of VEC and Vcn were measured using enzyme-linked immunosorbent assays. Results The serum VEC and Vcn concentrations were significantly higher in participants with AAD than in healthy controls. Receiver operating characteristic analysis generated areas under the curves for VEC and Vcn that were diagnostic for AAD (0.604 and 0.665, respectively). The optimal cut-off values were 3.986 ng/µL and 128.1 pg/mL, the sensitivities were 43.0% and 35.0%, and the specificities were 73.3% and 90.0%, respectively. In addition, the use of a combination of serum VEC and Vcn increased the AUC to 0.739, with a sensitivity of 56.0% and a specificity of 76.7%. A high serum Vcn concentration was associated with a higher risk of poor visceral malperfusion in participants with AAD (odds ratio [OR] = 1.007, 95% confidence interval [CI]: 1.001–1.013, p = 0.014). In participants with refractory pain, the adjusted OR for the serum VEC concentration increased to 1.172 (95% CI: 1.010–1.361; p = 0.036), compared with participants without refractory pain. Conclusion This study is the first to show the diagnostic value of serum VEC and Vcn for AAD and their relationships with the clinical characteristics of patients with AAD. Thus, VEC and Vcn are potential serum markers of AD.

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“…Tr-J mice sciatic nerve has marked alterations in junctional proteins including delocalized E-cadherin (Devaux & Scherer 2005). In turn, cumulative evidence indicates that adherens junctions proteins (E-cadherin, catenins, vinculin), some of which can act as NACos, may play a significant role in the myelination process (Tricaud et al 2005, Perrin-Tricaud et al 2007, Ye et al 2009, Peng et al 2010, Beppu et al 2015, Basak et al 2015. For example, Ecadherin enhances neuroregulin-1 (NRG1) signaling and promotes Schwann cell myelination (Basak et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #2 of "Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model (v0.1)"

2017

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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

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Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy

Cited by 9 publications

References 35 publications

Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model

High serum VE-cadherin and vinculin concentrations are markers of the disruption of vascular integrity during acute aortic dissection

Peer Review #2 of "Poly(ADP-ribosylation) is present in murine sciatic nerve fibers and is altered in a Charcot-Marie-Tooth-1E neurodegenerative model (v0.1)"

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