NLR-1/CASPR Anchors F-Actin to Promote Gap Junction Formation

Meng, Lingfeng; Yan, Dong

doi:10.1016/j.devcel.2020.10.020

Cited by 15 publications

(10 citation statements)

References 103 publications

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“…We next attempted to understand the mechanisms of UNC-9 localization in the DD neurons by examining the mutants of known regulators of gap junction localization. In the nerve ring, clustered UNC-9 localization depends on NLR-1/CASPR (Meng and Yan, 2020). In vertebrates, ZO-1 tight junction protein plays crucial roles in gap junction plaque formation.…”

Section: Resultsmentioning

confidence: 99%

Channel-independent function of UNC-9/INX in spatial arrangement of GABAergic synapses in C. elegans

Hendi

Niu

Snow

et al. 2022

Preprint

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Precise synaptic connection of neurons with their targets is essential for the proper functioning of the nervous system. A plethora of signaling pathways act in concert to mediate the precise spatial arrangement of synaptic connections. Here we show a novel role for a gap junction protein in controlling tiled synaptic arrangement in the GABAergic motor neurons in C. elegans, in which their axons and synapses overlap minimally with their neighboring neurons within the same class. We found that while EGL-20/Wnt controls axonal tiling, their presynaptic tiling is mediated by a gap junction protein UNC-9/Innexin, that is localized at the presynaptic tiling border between neighboring DD neurons. Strikingly, the gap junction channel activity of UNC-9 is dispensable for its function in controlling tiled presynaptic patterning. While gap junctions are crucial for the proper functioning of the nervous system as channels, our finding uncovered the novel channel-independent role of UNC-9 in synapse patterning.

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Section: Resultsmentioning

confidence: 99%

Channel-independent function of UNC-9/INX in spatial arrangement of GABAergic synapses in C. elegans

Hendi

Niu

Snow

et al. 2022

Preprint

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“…Six identical or different Cx subtypes can form one and a half channels, and two half channels can be docked to form a gap connection (Caufriez et al., 2020). The main function of half‐channel and gap junction is to transfer information, small molecules and ions between cells, thus regulating important processes such as cell growth, differentiation and apoptosis (Epifantseva & Shaw, 2018; Meng & Yan, 2020). Gap27 is a Cx43 mimic peptide that inhibits the activity and function of half‐channel and gap junctions (Caufriez et al., 2020; Faniku et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of gap junction communication between cells can induce apoptosis of corpus cavernosum smooth muscle in guinea pigs

et al. 2021

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In this study, we aimed to investigate the effect of gap junction (GJ) on apoptosis of smooth muscle. Forty adult male guinea pigs were randomly divided into four groups with 10 guinea pigs in each group. Adeno‐associated virus (AAV) and Gap27 were injected at the root of the corpus cavernosum. Two weeks later, the corpus cavernosum tissue was taken to be tested. The expression of Cx43 and α‐SMC protein was detected by immunofluorescence and Western blotting. The content of corpus cavernosum smooth muscle was detected by Masson trichrome staining. Apoptosis was detected by TUNEL staining and Western blotting. The results showed that Gap27 did not affect Cx43 but decreased the expression of smooth muscle. The results of TUNEL staining and detection of apoptosis‐related proteins showed that apoptosis was induced by Gap27. In addition, we found that corpus cavernosum injection of AAV could induce obvious apoptosis. In this study, we examined the effect of inhibition of gap junction on smooth muscle, and suggested that the decrease of gap junction function may be a potential mechanism of smooth muscle apoptosis.

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“…13 The contactin-associated protein 1 (CNTNAP1, also known as CASPR1) was originally identified as a vital cell-adhesion protein belonging to the neurexin superfamily. 14 CNTNAP1 participated in gap junction formation and neuronal development 15,16 as it can bind to Cntn1, 17 native prion protein, 18 and neurofascin. 19,20 Downregulated CASPR1 expression was related to the axonal demyelination in multiple sclerosis.…”

Section: Introductionmentioning

confidence: 99%

M2‐polarization‐related CNTNAP1 gene might be a novel immunotherapeutic target and biomarker for clear cell renal cell carcinoma

Meng

et al. 2022

IUBMB Life

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Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies, characterized by high mortality rate in urology. Unfortunately, reliable biomarkers for ccRCC diagnosis and prognosis remain lacking. Contactin‐associated protein 1 (CNTNAP1) has yet to be thoroughly investigated in cancer, especially its relationship with immune infiltration or clinical outcomes of ccRCC. Here, we explored The Cancer Genome Atlas Kidney Clear Cell Carcinoma database (TCGA‐KIRC) for prognostic significance, differential expression, and probable mechanism of CNTNAP1. The aberrant CNTNAP1 expression was also validated by the International Cancer Genome Consortium (ICGC) and ccRCC clinic samples. We used Database for Annotation, Visualization, and Integrated Discovery to perform the GO and KEGG enrichment. TIMER database was further utilized to assess its correlation with immune infiltration in ccRCC. The CellMiner database was used to analyze the relationship between CNTNAP1 expression and drug sensitivity. Results showed CNTNAP1 was upregulated in TCGA‐KIRC, ICGC, and clinic samples. And CNTNAP1 expression was positively related to infiltration levels of cancer‐associated fibroblast, regulatory T cells, and myeloid‐derived suppressor cells, while negatively related to eosinophils. Furthermore, we observed CNTNAP1 was appreciably positively associated with alternatively activated macrophage (M2) in ccRCC. Finally, high CNTNAP1 expression was negatively correlated with nilotinib, crizotinib, eribulin mesylate, and vinorelbine. Collectively, these results strongly suggest that CNTNAP1 might act as an immunotherapeutic target and a promising novel biomarker for ccRCC.

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NLR-1/CASPR Anchors F-Actin to Promote Gap Junction Formation

Cited by 15 publications

References 103 publications

Channel-independent function of UNC-9/INX in spatial arrangement of GABAergic synapses in C. elegans

Channel-independent function of UNC-9/INX in spatial arrangement of GABAergic synapses in C. elegans

Inhibition of gap junction communication between cells can induce apoptosis of corpus cavernosum smooth muscle in guinea pigs

M2‐polarization‐related CNTNAP1 gene might be a novel immunotherapeutic target and biomarker for clear cell renal cell carcinoma

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