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K+ channel complexes: assembly, trafficking and function

K 通道复合物：组装、运输和功能

基本信息

批准号：
9204883
负责人：
WILLIAM R KOBERTZ
金额：
$ 4.58万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-01 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9204883
关键词：
Action Potentials Affect Animals Arrhythmia Auditory Biogenesis Carbohydrate Chemistry Carbohydrates Cardiac Cations Cell membrane Cell surface Cells Chloride Ion Chlorides Complex Consensus Coupled Data Detection Diffuse Disease Engineering Ensure Event Extracellular Space Family Funding Future Genetic Glycocalyx Goals Golgi Apparatus Health Human Hydroxyl Radical Individual Integral Membrane Protein Ion Channel Ions Kinetics Laboratories Life Link Long QT Syndrome Lung diseases Measures Membrane Membrane Proteins Molecular Multiprotein Complexes Muscle Mutation Neurologic Pathway interactions Peptide Signal Sequences Peptides Pharmaceutical Preparations Phase Physiologic pulse Physiological Polysaccharides Post-Translational Protein Processing Potassium Potassium Channel Process Protein Isoforms Proteins Protons RNA Interference Radioactive Reporting Research Site Sulfhydryl Compounds Testing Thick Voltage-Gated Potassium Channel Work antiporter base congenital deafness disease-causing mutation fluorophore glycosylation nanometer prevent research study sensor sugar trafficking

项目摘要

The long-term goal of this research is to elucidate the molecular and cellular mechanisms that ensure potassium (K+) channels assemble with the appropriate membrane-embedded regulatory subunits for proper physiological function. N-glycosylation is a vital co- and post-translational modification that facilitates the assembly and trafficking of K+ channel subunits. Mutations that block glycosylation of KCNE K+ regulatory subunits have been directly linked to the genetic and drug-induced forms of cardiac arrhythmias (Long QT Syndrome). Accordingly, the two aims of this proposal investigate K+ channel subunit glycosylation in the ER, Golgi and plasma membrane: (1) We will determine the molecular and cellular bases of K+ channel subunit co- and post-translational N-glycosylation. (2) We will reengineer the cell's glycocalyx to fluorescently visualize K+ efflux from living cells.

这项研究的长期目标是阐明确保钾 (K+) 通道与适当的膜嵌入调节亚基组装，以实现适当的功能生理功能。 N-糖基化是一种重要的翻译共修饰和翻译后修饰，可促进 K+通道亚基的组装和运输。阻止 KCNE K+ 调节糖基化的突变亚基与遗传和药物诱导的心律失常（长 QT 综合症）。因此，该提案的两个目标是研究 ER 中的 K+ 通道亚基糖基化，高尔基体和质膜：（1）我们将确定K+通道亚基共-的分子和细胞基础和翻译后 N-糖基化。 (2) 我们将重新设计细胞的糖萼以荧光可视化 K+ 从活细胞流出。