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
-
Neglected Tropical Protozoan Diseases: Drug Repositioning as a Rational Option
Current Topics in Medicinal Chemistry Atrial Fibrillation During or After TAVI: Incidence, Implications and Therapeutical Considerations
Current Pharmaceutical Design COX-Inhibiting Nitric Oxide Donors (CINODs): Potential Benefits on Cardiovascular and Renal Function
Cardiovascular & Hematological Agents in Medicinal Chemistry Non Coding RNA in Muscle Differentiation and Disease
MicroRNA Protein-Protein Interactions: Recent Progress in the Development of Selective PDZ Inhibitors
Current Chemical Biology Intracoronary Injection of Drugs to Treat No – Reflow Phenomenon and Microcirculatory Dysfunction
Cardiovascular & Hematological Agents in Medicinal Chemistry Cardiac Calmodulin Kinase: A Potential Target for Drug Design
Current Medicinal Chemistry Vascular Inflammation and Atherosclerosis: The Role of Estrogen Receptors
Current Medicinal Chemistry Regular Physical Activity and Vascular Aging
Current Pharmaceutical Design Bivalirudin or Heparin Treatment During Transcatheter Valve Interventions: Where are we Now?
Current Pharmaceutical Design Simultaneous Separation, Quantitation, and Determination of the Dissociation Constant of Five Components of Ixeris sonchifolia by Microemulsion Electrokinetic Chromatography
Current Pharmaceutical Analysis Clinical Use of Clopidogrel
Current Pharmaceutical Design The Role of ABC Transporters in Protecting Cells from Bilirubin Toxicity
Current Pharmaceutical Design SIRT1, a Calorie Restriction Mimetic, in a New Therapeutic Approach for Type 2 Diabetes Mellitus and Diabetic Vascular Complications
Endocrine, Metabolic & Immune Disorders - Drug Targets Why are People with “Poor Lung Function” At Increased Atherothrombotic Risk?A Critical Review with Potential Therapeutic Indications
Current Vascular Pharmacology Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease
Current Pharmaceutical Design Neurotrophic and Neuroprotective Effects of Muscle Contraction
Current Pharmaceutical Design Therapeutic Intervention in Cancer and Chronic Viral Infections: Antibody Mediated Manipulation of PD-1/PD-L1 Interaction
Reviews on Recent Clinical Trials Discovery of MAO-B Inhibitors - Present Status and Future Directions Part I: Oxygen Heterocycles and Analogs
Mini-Reviews in Medicinal Chemistry Targeting IGF-I, IGFBPs and IGF-I Receptor System in Cancer: The Current and Future in Breast Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery