Abstract
Important roles for connexins have emerged from studies linking connexin mutations to human disease. Use of connexins tagged with GFP have provided a clearer picture of the mechanisms that govern connexin channel function and it is now evident that functional forms of connexin channel include cell-cell channels and unapposed hemichannels. Clustering appears to be a requirement for opening of cell-cell channels and suggests that dynamic changes occur in plaques (clusters) as they form and grow that are critical for channel function. In particular, recruitment or generation of ‘silent’ channels has gained support as a mechanism by which coupling can be dynamically regulated within formed plaques. Two distinct voltage sensitive gating mechanisms appear to be built -into each hemichannel, one putatively located at the cytoplasmic entrance and the other at the extracellular end, each differing in sensitivity, kinetics and degree of channel/hemichannel closure. The extracellular gate may also be that whic h opens unapposed hemichannels in the plasma membrane and be the final target of many known chemical agents that act as uncouplers of cell-cell communication. An understanding of the structural requirements for regulation via gating and clustering represents an important preclinical step in the design of therapeutic agents to treat disorders arising from connexin channel and hemichannel dysfunction.
Current Drug Targets
Title: Connexin-GFPs Shed Light on Regulation of Cell-Cell Communication by Gap Junctions
Volume: 3 Issue: 6
Author(s): Vytas K. Verselis and Feliksas F. Bukauskas
Affiliation:
Abstract: Important roles for connexins have emerged from studies linking connexin mutations to human disease. Use of connexins tagged with GFP have provided a clearer picture of the mechanisms that govern connexin channel function and it is now evident that functional forms of connexin channel include cell-cell channels and unapposed hemichannels. Clustering appears to be a requirement for opening of cell-cell channels and suggests that dynamic changes occur in plaques (clusters) as they form and grow that are critical for channel function. In particular, recruitment or generation of ‘silent’ channels has gained support as a mechanism by which coupling can be dynamically regulated within formed plaques. Two distinct voltage sensitive gating mechanisms appear to be built -into each hemichannel, one putatively located at the cytoplasmic entrance and the other at the extracellular end, each differing in sensitivity, kinetics and degree of channel/hemichannel closure. The extracellular gate may also be that whic h opens unapposed hemichannels in the plasma membrane and be the final target of many known chemical agents that act as uncouplers of cell-cell communication. An understanding of the structural requirements for regulation via gating and clustering represents an important preclinical step in the design of therapeutic agents to treat disorders arising from connexin channel and hemichannel dysfunction.
Export Options
About this article
Cite this article as:
Vytas K. Verselis and Feliksas F. Bukauskas , Connexin-GFPs Shed Light on Regulation of Cell-Cell Communication by Gap Junctions, Current Drug Targets 2002; 3 (6) . https://dx.doi.org/10.2174/1389450023347272
DOI https://dx.doi.org/10.2174/1389450023347272 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Perinatal Heart Programming: Long-term Consequences
Current Medicinal Chemistry A Genetic Dissection of Antipsychotic Induced Movement Disorders
Current Medicinal Chemistry The Role of Endothelin System in Cardiovascular Disease and the Potential Therapeutic Perspectives of its Inhibition
Current Topics in Medicinal Chemistry Cardiac and Pulmonary Manifestations in the Antiphospholipid Syndrome
Current Rheumatology Reviews Discovering Natural Product Modulators to Overcome Multidrug Resistance in Cancer Chemotherapy
Current Pharmaceutical Biotechnology The Acid Sphingomyelinase/Ceramide Pathway: Biomedical Significance and Mechanisms of Regulation
Current Molecular Medicine Management of Hypertension in Relation to Acute Coronary Syndromes and Revascularisation
Current Pharmaceutical Design New Medical Strategies for Midgut Carcinoids
Anti-Cancer Agents in Medicinal Chemistry Auto-Antibodies As Possible Markers and Mediators of Ischemic, Dilated, and Rhythmic Cardiopathies
Current Drug Targets Therapeutic Antibodies and Other Proteins Obtained by Molecular Display Technologies
Recent Patents on Biotechnology Plasma Glucose Concentrations and Cardiac Hypertrophy in Essential Hypertension
Current Hypertension Reviews Beneficial and Detrimental Effects of Antioxidants Use in Sports: How is it Balanced?
Current Nutraceuticals Nimodipine Reappraised: An Old Drug With a Future
Current Neuropharmacology Pulmonary Hypertension and Lung Transplantation
Current Hypertension Reviews Cardiovascular Risk Factors, Metabolic Complications, & the Natural Course of CKD in Children
Current Hypertension Reviews COVID-19 and Autoimmune Diseases: A Systematic Review of Reported Cases
Current Rheumatology Reviews The Ca2+-Activated K+ Channel of Intermediate Conductance:A Molecular Target for Novel Treatments?
Current Drug Targets Mesenchymal Stem Cells as a Source of Dopaminergic Neurons: A Potential Cell Based Therapy for Parkinson's Disease
Current Stem Cell Research & Therapy An In-Silico Investigation of Anti-Chagas Phytochemicals
Current Clinical Pharmacology Positive Social Interactions in a Lifespan Perspective with a Focus on Opioidergic and Oxytocinergic Systems: Implications for Neuroprotection
Current Neuropharmacology