Purpose: The lens is an avascular organ in which gap junctions provide a pathway for intercellular communication, which is vital to maintain lens transparency. Connexin43 (Cx43) is the main gap-junctional protein in lens epithelial cells. Phosphorylation of connexins is implicated in the regulation of intercellular communication. The objective of this report is to determine whether phosphorylation of Cx43 in lens epithelial cells alters its resistance to degradation by a proteasome dependent mechanism.
Methods: Primary cultures of LEC were incubated with protein kinase activator (TPA) and allowed to recover either in the presence or absence of proteasome or lysosome inhibitors. The contribution of the proteasome for the degradation of the phosphorylated form of Cx43 was further investigated by metabolic labeling with 32P or [35S]-methionine. Subcellular distribution of Cx43 was evaluated by immunofluorescence using antibodies directed against Cx43. Gap junctional intercellular communication was evaluated by transfer of the dye Lucifer yellow.
Results: Inhibitors of proteasome and lysosome both stabilize Cx43, while proteasome inhibitors preferentially stabilize the phosphorylated form of the protein. Pulse chase experiments with 32P or [35S]-methionine show that while phosphorylation destabilizes Cx43, proteasome inhibitors stabilize the phosphorylated form of the protein. Intercellular communication is inhibited by TPA and can be restored by proteasome inhibitors, probably by preventing loss of Cx43 from the plasma membrane following treatment with TPA.
Conclusions: Our observations support a model in which the combined action of phosphorylation and protein degradation by a proteasome dependent mechanism contribute to regulate Cx43 stability in plasma membrane and intercellular communication through gap junctions, thus adding a novel level of regulation to intercellular communication in lens epithelial cells.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Cancer cells within tumors exhibit a wide range of phenotypic states driven by non-genetic mechanisms in addition to extensively studied genetic alterations. Conversions among cancer cell states can result in intratumoral heterogeneity which contributes to metastasis and development of drug resistance. However, mechanisms underlying the initiation and/or maintenance of such phenotypic plasticity are poorly understood.
View Article and Find Full Text PDFMicrobial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway.
View Article and Find Full Text PDFCellMsg: graph convolutional networks for ligand-receptor-mediated cell-cell communication analysis.
Brief Bioinform
November 2024
College of Computer Science and Electronic Engineering, Hunan University, Changsha 410082, China.
The role of cell-cell communications (CCCs) is increasingly recognized as being important to differentiation, invasion, metastasis, and drug resistance in tumoral tissues. Developing CCC inference methods using traditional experimental methods are time-consuming, labor-intensive, cannot handle large amounts of data. To facilitate inference of CCCs, we proposed a computational framework, called CellMsg, which involves two primary steps: identifying ligand-receptor interactions (LRIs) and measuring the strength of LRIs-mediated CCCs.
View Article and Find Full Text PDFFAP-targeted radioligand therapy with Ga/Lu-DOTA-2P(FAPI) enhance immunogenicity and synergize with PD-L1 inhibitors for improved antitumor efficacy.
J Immunother Cancer
January 2025
Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Background: Fibroblast activation protein (FAP)-targeted radioligand therapy, with immunomodulatory effects, has shown efficacy in both preclinical and clinical studies. We recently reported on a novel dimeric FAP-targeting radiopharmaceutical, Ga/Lu-DOTA-2P(FAPI), which demonstrated increased tumor uptake and prolonged retention in various cancers. However, further exploration is required to understand the therapeutic efficacy and underlying mechanisms of combining Ga/Lu-DOTA-2P(FAPI) radioligand therapy with PD-1/PD-L1 immunotherapy.
View Article and Find Full Text PDFIntercellular communication is crucial in the regulation of healthy aging via exosomes.
Pharmacol Res
January 2025
College of Biological and Food Engineering, Qujing Normal University, 655011, Qujing, Yunnan, China. Electronic address:
The hallmarks of aging encompass a variety of molecular categories (genomic, telomeric, and epigenetic), organelles (proteostasis, autophagy, and mitochondria), cellular components (including stem cells), systems (such as intercellular communication and chronic inflammation), and environmental factors (dysbiosis and nutrient sensing). These hallmarks play a crucial role in the aging process. Despite their intricate interconnections, the relationships among the hallmarks of aging remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!