Towards the Physiologic Function of MiRP-3

描述(申请人提供)：MCSD建议：研究MIRP-3的生理功能。 研究表明：钾离子通道催化K+离子跨细胞膜移动，其功能对细胞电活动和电解质平衡至关重要。许多K+通道受辅助亚单位蛋白的调节，这是正常生理功能所必需的，并使通道能够适应环境条件的变化。本申请描述了水貂相关多肽超家族中的一个新成员--β亚基MIRP-3的研究，它可以调节这种K+通道的特性。我们提出的初步证据表明，MIRP-3在调节血管平滑肌功能以及肾脏钾分泌和酸碱平衡方面发挥作用。我们提出了一个研究MIRP-3和一个生理相关伙伴的计划。将评估MIRP-3对K+通道的影响，以及这种调制如何影响生理过程。候选人：丹尼尔·I·利维博士，受训为离子通道生理学家。宾夕法尼亚。Sch.)，这促使他决定选择在内科(大学医院)实习。(宾夕法尼亚州)和肾脏学子专业培训(耶鲁)。他现在是芝加哥大学肾脏学部的一名讲师。他的职业目标是经营一个基础研究实验室，研究离子通道功能的机制原理及其对人类疾病的影响。这项建议是为了支持他在生物物理学、生物化学和分子遗传学领域的职业发展，使他能够成为一名独立的研究员和学术上可行的临床医生兼科学家。 环境：主要赞助人史蒂夫·戈尔茨坦博士是钾通道研究和离子通道病变方面的领先研究员。他的实验室拥有丰富的生物物理、分子生物学和分子遗传学专业知识，首次鉴定并表达了三种与水貂相关的多肽。芝加哥大学的医学系和神经生物学、药理学和生理学系包括一批国际公认的离子通道研究人员。

DESCRIPTION (provided by applicant): MCSD Proposal: Towards the physiologic function of MiRP-3. The research: Potassium channels catalyze the movement of K+ ions across the cell membrane, and their function is essential for cellular electrical activity and electrolyte homeostasis. Many K+ channels are regulated by accessory-subunit proteins, which can be required for normal physiologic function and allow for the channels to adapt to changes of environmental conditions. This application describes the study of the beta subunit MiRP-3, a novel member of the MinK-related peptide superfamily, which can modulate the properties of such K+ channels. We present preliminary evidence that suggests a role for MiRP-3 in modulating vascular smooth-muscle function as well as renal potassium secretion and acid-base homeostasis. We propose a plan to study MiRP-3 and a physiologically relevant partner. MiRP-3 will be evaluated for its effects on K+ channels and how such modulation can influence physiologic processes. The candidate: Dr. Daniel I. Levy trained as an ion-channel physiologist (Univ. Penn. Sch. Med.), which motivated his decision to choose a residency in Internal Medicine (Hosp. Univ. Pennsylvania) and subspecialty training in Nephrology (Yale). He is now an Instructor in the Nephrology section at the University of Chicago. His career goal is to run a basic research laboratory investigating the mechanistic principles of ion channel function and their implications for human diseases. This proposal is submitted to support his career development in the disciplines of biophysics, biochemistry, and molecular genetics, to enable him to become an independent investigator and academically viable clinician-scientist. The environment: The primary sponsor, Dr. Steve Goldstein, is a leading investigator in potassium channel research and ion channelopathies. The first three MinK-related peptides were identified and expressed in his laboratory, which is rich in biophysical, molecular biology, and molecular genetics expertise. The Department of Medicine and the Department of Neurobiology, Pharmacology & Physiology at the University of Chicago include an internationally recognized cadre of ion channel researchers.