CYLD deubiquitinates plakoglobin to promote Cx43 membrane targeting and gap junction assembly in the heart

Xie, Wei; Gao, Siqi; Yang, Yunfan; Li, Hongjie; Zhou, Junyan; Chen, Mingzhen; Yang, Song; Zhang, Yijun; Zhang, Liang; Meng, Xiao-Qian; Xie, Songbo; Liu, Min; Li, Dengwen; Chen, Yan; Zhou, Jun

doi:10.1016/j.celrep.2022.111864

Cited by 9 publications

(10 citation statements)

References 60 publications

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“…Similarly, Dsg2 and Pkp2 probably also influence the functional properties of these channels through their association with Nav1.5 178–180 . In a recent study, Pg deubiquitination enhanced its interaction with the Dp and end‐binding protein 1 complex, promoting the microtubule‐dependent transport of Cx43 181 …”

Section: Camp Induces Positive Adhesiotropy In Cardiomyocytesmentioning

confidence: 97%

“…[178][179][180] In a recent study, Pg deubiquitination enhanced its interaction with the Dp and end-binding protein 1 complex, promoting the microtubule-dependent transport of Cx43. 181 The downstream mechanisms of cAMP-mediated positive adhesiotropy include PKA-mediated Pg-S665 phosphorylation and ERK1/2 182 (Figure 4), the latter of which was dependent on Pg, Dp, and Dsg2 in vitro. Interestingly, the role of ERK1/2 in desmosomal adhesion contrasts in keratinocytes compared to cardiomyocytes, as ERK1/2 inhibition rather than activation was proven beneficial for desmosomal adhesion in keratinocytes.…”

Section: Camp Induces Positive Adhesiotropy In Cardiomyocytesmentioning

confidence: 99%

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cAMP: A master regulator of cadherin‐mediated binding in endothelium, epithelium and myocardium

et al. 2023

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Regulation of cadherin‐mediated cell adhesion is crucial not only for maintaining tissue integrity and barrier function in the endothelium and epithelium but also for electromechanical coupling within the myocardium. Therefore, loss of cadherin‐mediated adhesion causes various disorders, including vascular inflammation and desmosome‐related diseases such as the autoimmune blistering skin dermatosis pemphigus and arrhythmogenic cardiomyopathy. Mechanisms regulating cadherin‐mediated binding contribute to the pathogenesis of diseases and may also be used as therapeutic targets. Over the last 30 years, cyclic adenosine 3′,5′‐monophosphate (cAMP) has emerged as one of the master regulators of cell adhesion in endothelium and, more recently, also in epithelial cells as well as in cardiomyocytes. A broad spectrum of experimental models from vascular physiology and cell biology applied by different generations of researchers provided evidence that not only cadherins of endothelial adherens junctions (AJ) but also desmosomal contacts in keratinocytes and the cardiomyocyte intercalated discs are central targets in this scenario. The molecular mechanisms involve protein kinase A‐ and exchange protein directly activated by cAMP‐mediated regulation of Rho family GTPases and S665 phosphorylation of the AJ and desmosome adaptor protein plakoglobin. In line with this, phosphodiesterase 4 inhibitors such as apremilast have been proposed as a therapeutic strategy to stabilize cadherin‐mediated adhesion in pemphigus and may also be effective to treat other disorders where cadherin‐mediated binding is compromised.

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Section: Camp Induces Positive Adhesiotropy In Cardiomyocytesmentioning

confidence: 97%

Section: Camp Induces Positive Adhesiotropy In Cardiomyocytesmentioning

confidence: 99%

cAMP: A master regulator of cadherin‐mediated binding in endothelium, epithelium and myocardium

et al. 2023

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“… 4 In the past, it was thought that bone marrow adipocytes (BMAds) were only used to fill the extra space of bone marrow cavity when bone mass was reduced or hematopoiesis was damaged, but increasing evidence showed that BMAds, as an important part of hematopoietic microenvironment, affect the self‐renewal and differentiation of HSCs by secreting adiponectin, leptin, prostaglandin, IL‐6, and other fat‐derived factors. 5 , 6 , 7 , 8 , 9 , 10 Moreover, macrophages in white adipose tissue (WAT) can regulate metabolic homeostasis by promoting the utilization of glucose by adipocytes under normal conditions, and can affect sympathetic nerve tension, control lipid storage and release, and increase energy expenditure. 11 , 12 When obesity occurs, many cytokines can activate macrophages in WAT, causing the imbalance of sugar, fat and energy metabolism, and inducing insulin resistance and adipose tissue inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Marrow adipose tissue (MAT) is located in the marrow cavity, accounting for more than 10% of the total body fat in healthy adults over 25 years old 4 . In the past, it was thought that bone marrow adipocytes (BMAds) were only used to fill the extra space of bone marrow cavity when bone mass was reduced or hematopoiesis was damaged, but increasing evidence showed that BMAds, as an important part of hematopoietic microenvironment, affect the self‐renewal and differentiation of HSCs by secreting adiponectin, leptin, prostaglandin, IL‐6, and other fat‐derived factors 5–10 . Moreover, macrophages in white adipose tissue (WAT) can regulate metabolic homeostasis by promoting the utilization of glucose by adipocytes under normal conditions, and can affect sympathetic nerve tension, control lipid storage and release, and increase energy expenditure 11,12 .…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue and hematopoiesis: Friend or foe?

Liu

2023

Clinical Laboratory Analysis

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Aim Hematopoietic stem cells are the origin of all hematopoietic cells. They have the self‐renewal ability and can differentiate into various blood cells. In physiological state, most of the hematopoietic stem cells are dormant, and only a few cells proliferate to maintain hematopoietic homeostasis. Methods This precise steady‐state maintenance is regulated by complex mechanisms. Bone marrow adipocytes make up half of all cells in the bone marrow cavity, a feature that has attracted the attention of researchers from multiple fields. The adipocyte density within marrow increases during aging and obesity. Results Recent studies have shown that bone marrow adipocytes play important roles in regulating hematopoiesis, but the effects of bone marrow adipocytes on hematopoiesis are often conflicting. Bone marrow adipocytes, participating in the formation of bone marrow hematopoietic microenvironment, influence hematopoiesis positively or negatively. In addition, other adipose tissue, especially white adipose tissue, also regulates hematopoiesis. Conclusion In this review, we describe the role of adipose tissue in hematological malignancies, which may be useful for understanding hematopoiesis and the pathogenesis of related diseases.

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“…In addition, CYLD participates in regulating a large variety of cell processes, including cell cycle progression, cell migration, chemotherapy drug sensitivity, and ciliogenesis (Hu et al, 2022; Ran et al, 2021; Yang & Zhou, 2016; Yang, Chen, et al, 2021). Cyld knockout (KO) mice exhibited exacerbated hearing impairment and cardiac mortality (Xie et al, 2022; Yang, Ma, et al, 2021). Accumulating evidence has revealed that CYLD acts as a pivotal negative regulator of RANK signaling on preosteoclasts, inhibiting ubiquitination of the E3‐ubiquitin ligase TRAF6 and activating downstream signaling pathways (Asagiri & Takayanagi, 2007; Boyle et al, 2003; Durán et al, 2004; Teitelbaum & Ross, 2003).…”

Section: Introductionmentioning

confidence: 99%

CYLD inhibits osteoclastogenesis to ameliorate alveolar bone loss in mice with periodontitis

Cao

Zhang

et al. 2023

Journal Cellular Physiology

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Periodontitis is a chronic immune inflammatory disease that can lead to the destruction and loss of the tooth‐supporting apparatus. During this process, the balance between bone absorption mediated by osteoclasts and bone formation mediated by osteoblasts is damaged. Consistent with previous studies, we observed that depletion of cylindromatosis (CYLD) resulted in an osteoporotic bone phenotype. However, the effect of CYLD deficiency on periodontitis is undetermined. Here, we investigated whether CYLD affects periodontal tissue homeostasis in experimental periodontitis in Cyld knockout (KO) mice, and we explored the underlying mechanisms. Interestingly, we discovered significant alveolar bone density loss and severely reduced alveolar bone height in Cyld KO mice with experimentally induced periodontitis. We observed increased osteoclast number and activity in both the femurs and alveolar bones, accompanied by the downregulation of osteogenesis genes and upregulation of osteoclastogenesis genes of alveolar bones in ligatured Cyld KO mice. Taken together, our findings demonstrate that the deletion of CYLD in mice plays a vital role in the pathogenesis of periodontal bone loss and suggest that CYLD might exert an ameliorative effect on periodontal inflammatory responses.

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CYLD deubiquitinates plakoglobin to promote Cx43 membrane targeting and gap junction assembly in the heart

Cited by 9 publications

References 60 publications

cAMP: A master regulator of cadherin‐mediated binding in endothelium, epithelium and myocardium

cAMP: A master regulator of cadherin‐mediated binding in endothelium, epithelium and myocardium

Adipose tissue and hematopoiesis: Friend or foe?

CYLD inhibits osteoclastogenesis to ameliorate alveolar bone loss in mice with periodontitis

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