tailieunhanh - Báo cáo Y học: The cytoplasmic C-terminus of the sulfonylurea receptor is important for KATP channel function but is not key for complex assembly or trafficking

ATP-sensitive K + channels are an octameric assembly of two proteins, a sulfonylurea receptor (SUR1)and an ion conducting subunit (Kir ). We have examined the role of the C-terminus of SUR1 by expressing a series of truncation mutants together with stably in HEK293 cells. Bio-chemical analyses using coimmunoprecipitation indicate that SUR1 deletionmutants assemble and that a SUR1 deletion mutant binds glibenclamide with high affin-ity. | Eur. J. Biochem. 269 5303-5313 2002 FEBS 2002 doi The cytoplasmic C-terminus of the sulfonylurea receptor is important for Katp channel function but is not key for complex assembly or trafficking Jonathan P. Giblin Kathryn Quinn and Andrew Tinker Centre for Clinical Pharmacology Department of Medicine University College London The Rayne Institute UK ATP-sensitive K channels are an octameric assembly of two proteins a sulfonylurea receptor SUR1 nnd nn ion conducting subunit Kir . We have examined the role of the C-terminus of SUR1 by expressing a series of truncation mutants together with stably in HEK293 cells. Biochemical analyses using coimmunoprecipitation indicate that SUR1 deletion mutants and assemble and that a SUR1 deletion mutant binds glibenclamide with high affinity. Electrophysiological recordings indicate that ATP sensitivity is normal but the response of the mutant channel complexes to tolbutamide MgADP and diazoxide is dis turbed. Quantitative immunofluorescence and cell surface biotinylation supports the idea that there is little disturbance in the efficiency of trafficking. Our data show that deletions of the C-terminal most cytoplasmic domain of SUR1 can result in functional channels at the plasma membrane in mammalian cells that have an abnormal response to physiological and pharmacological agents. Keywords K channel inward rectifier ATP-sensitive trafficking and assembly sulfonylurea receptor. ATP-sensitive potassium channels KATP are present in the plasma membrane of a number of tissues and are also present in endomembranes such as mitochondria. They have been proposed to be involved in a number of physiological and pathophysiological processes and form a link between cellular metabolism and membrane excitability. For example in the pancreas KATP regulates insulin release and in vascular smooth muscle it is regulated by vasodilators and influences blood flow in certain vascular beds. Katp is an

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• intermediate cells
• cell proliferation
• medical analysis
• thesis report
• medical report
• medical knowledge
• medical research
• analysis of cytoplasmic
• environmental medicine
• raccoon experiments
• Content and Language Integrated Learning
• Analysis of term extraction for English
• English medical texts
• Vietnamese medical experts
• Educational philosophy across Europe
• Medical image analysis
• Computer aided diagnosis
• FLAIR magnetic resonance imaging
• Realistic lesion insertion
• Medical data augmentation
• Diffuse lung diseases
• Tomosynthesis imaging
• Spinal abnormalities
• Health informatics
• Medical microwave imaging
• statements and documents scientific reports
• medical reports
• clinical trials
• medical management
• health care
• scientific research
• health policy
• pathology
• anatomy
• health education