Mutant cochlear connexins associated with deafness
与耳聋相关的突变耳蜗连接蛋白
基本信息
- 批准号:7147778
- 负责人:
- 金额:$ 10.15万
- 依托单位:
- 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:2005-09-01 至 2007-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant): Gap junctions are aqueous channels permeable to ions and hydrophilic molecules of Mr < 1,000. Each gapjunctional channel is formed by head-to-head association of two connexons (connexin hexamers), one from each of the adjacent cells. The cochlea (responsible for mechano-transduction of sound waves into electrical impulses) has a highly-developed gap-junctional network that is essential for hearing. In most cells of the normal cochlea gap-junctional channels are heteromeric assemblies formed by the connexins Cx26 and Cx30. Infant deafness due to mutations of Cx26 is very common and our long-term objective is to elucidate at the molecular level the mechanisms by which mutations of connexins cause deafness. The properties of wild-type Cx26, Cx30 and heteromeric Cx26/Cx30 connexons, and the effects of mutations that cause deafness on the properties of heteromeric connexons that include wild-type connexins, are poorly understood. This is in part due to the fact that the few groups that have carried out functional experiments on Cx26 and Cx30 mutants work with complex systems, performing measurements that depend on the gapjunctional communication between two neighboring cells. This kind of experiments is essential to understand the effects of the mutations, but cannot fully address the molecular mechanism of the alterations. The specific aims of this proposal are: 1) to develop an expression/purification/reconstitution system that yields large amounts of functional wild-type and mutant Cx26 and Cx30, and 2) to test the usefulness of the purified connexon system to determine the functional properties of connexons formed by wild-type and mutant connexins. We will adapt the methodology that we developed recently for Cx43, which should allow us to obtain large amounts of functional Cx26 and Cx30, and connexin mutants. We will study the permeability properties of wild-type and mutant homomeric Cx26 and Cx30 connexons and heteromeric Cx26/Cx30 connexons formed by wild-type connexins as well as connexons containing Cx26 or Cx30 mutants. An integrative approach comparing the properties of gap- junctional channels and connexons will allow us to determine whether specific mutations alter gap-junctional communication at the level of the gap-junctional channel (e.g., docking between GJH) or connexon (e.g., non-permeable connexons).
描述(由申请人提供):间隙连接是可渗透Mr <1,000的离子和亲水性分子的水通道。每个缝隙连接通道由两个连接子(连接蛋白六聚体)的头对头结合形成,每个连接子来自相邻细胞中的一个。耳蜗(负责将声波机械转换为电脉冲)具有高度发达的间隙连接网络,这对听力至关重要。在正常耳蜗的大多数细胞中,缝隙连接通道是由连接蛋白Cx 26和Cx 30形成的异聚体。婴儿耳聋由于Cx 26的突变是非常常见的,我们的长期目标是阐明在分子水平上的机制,连接蛋白的突变导致耳聋。野生型Cx 26、Cx 30和异聚Cx 26/Cx 30连接子的性质,以及导致耳聋的突变对包括野生型连接蛋白的异聚连接子性质的影响,知之甚少。这在一定程度上是由于这样一个事实,即对Cx 26和Cx 30突变体进行功能实验的少数小组使用复杂的系统,进行依赖于两个相邻细胞之间的间隙连接通信的测量。此类实验对于了解突变的影响至关重要,但无法完全解决改变的分子机制。该提议的具体目的是:1)开发产生大量功能性野生型和突变型Cx 26和Cx 30的表达/纯化/重建系统,和2)测试纯化的连接子系统的有用性以确定由野生型和突变型连接蛋白形成的连接子的功能特性。我们将采用我们最近开发的用于Cx43的方法,这将使我们能够获得大量功能性Cx 26和Cx 30以及连接蛋白突变体。我们将研究野生型和突变体的同源Cx 26和Cx 30连接子和由野生型连接蛋白以及含有Cx 26或Cx 30突变体的连接子形成的异源Cx 26/Cx 30连接子的通透性特性。比较间隙连接通道和连接子的性质的综合方法将允许我们确定特定突变是否在间隙连接通道的水平上改变间隙连接通讯(例如,GJH之间的对接)或连接子(例如,非渗透性连接子)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
GUILLERMO A ALTENBERG其他文献
GUILLERMO A ALTENBERG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('GUILLERMO A ALTENBERG', 18)}}的其他基金
Architecture of the transmembrane pore formed by connexin 43
连接蛋白 43 形成的跨膜孔的结构
- 批准号:
7935723 - 财政年份:2009
- 资助金额:
$ 10.15万 - 项目类别:
Architecture of the transmembrane pore formed by connexin 43
连接蛋白 43 形成的跨膜孔的结构
- 批准号:
7900946 - 财政年份:2007
- 资助金额:
$ 10.15万 - 项目类别:
Architecture of the transmembrane pore formed by connexin 43
连接蛋白 43 形成的跨膜孔的结构
- 批准号:
8080841 - 财政年份:2007
- 资助金额:
$ 10.15万 - 项目类别:
Architecture of the transmembrane pore formed by connexin 43
连接蛋白 43 形成的跨膜孔的结构
- 批准号:
7475614 - 财政年份:2007
- 资助金额:
$ 10.15万 - 项目类别:
Architecture of the transmembrane pore formed by connexin 43
连接蛋白 43 形成的跨膜孔的结构
- 批准号:
7316876 - 财政年份:2007
- 资助金额:
$ 10.15万 - 项目类别:
Architecture of the transmembrane pore formed by connexin 43
连接蛋白 43 形成的跨膜孔的结构
- 批准号:
7634511 - 财政年份:2007
- 资助金额:
$ 10.15万 - 项目类别:
Mutant cochlear connexins associated with deafness
与耳聋相关的突变耳蜗连接蛋白
- 批准号:
6968536 - 财政年份:2005
- 资助金额:
$ 10.15万 - 项目类别:
Mutant cochlear connexins associated with deafness
与耳聋相关的突变耳蜗连接蛋白
- 批准号:
7448886 - 财政年份:2005
- 资助金额:
$ 10.15万 - 项目类别:
Development of Genetically-Encoded Glucose Sensors
基因编码葡萄糖传感器的开发
- 批准号:
6569915 - 财政年份:2003
- 资助金额:
$ 10.15万 - 项目类别:
Development of Genetically-Encoded Glucose Sensors
基因编码葡萄糖传感器的开发
- 批准号:
6691020 - 财政年份:2003
- 资助金额:
$ 10.15万 - 项目类别:
相似海外基金
The European Xenopus Resource Centre
欧洲爪蟾资源中心
- 批准号:
BB/X018601/1 - 财政年份:2023
- 资助金额:
$ 10.15万 - 项目类别:
Research Grant
Localized mitochondrial metabolic activity in Xenopus mesendoderm cells undergoing collective cell migration
爪蟾中内胚层细胞集体细胞迁移的局部线粒体代谢活性
- 批准号:
10751722 - 财政年份:2023
- 资助金额:
$ 10.15万 - 项目类别:
Conference: 19th International Xenopus Conference
会议:第19届国际爪蟾会议
- 批准号:
2323251 - 财政年份:2023
- 资助金额:
$ 10.15万 - 项目类别:
Standard Grant
Analysis of Congenital Hydrocephalus Genes in Xenopus
非洲爪蟾先天性脑积水基因分析
- 批准号:
10626955 - 财政年份:2022
- 资助金额:
$ 10.15万 - 项目类别:
In vivo persistence and immuno-pathogenesis of Mycobacterium abscessus in a new Xenopus tadpole model
脓肿分枝杆菌在新爪蟾蝌蚪模型中的体内持久性和免疫发病机制
- 批准号:
10350750 - 财政年份:2022
- 资助金额:
$ 10.15万 - 项目类别:
Analysis of Congenital Hydrocephalus Genes in Xenopus
非洲爪蟾先天性脑积水基因分析
- 批准号:
10502642 - 财政年份:2022
- 资助金额:
$ 10.15万 - 项目类别:
Development and function of the Xenopus tadpole retinotegmental projection
非洲爪蟾蝌蚪视网膜被盖投射的发育和功能
- 批准号:
2212591 - 财政年份:2022
- 资助金额:
$ 10.15万 - 项目类别:
Standard Grant