Mechanisms of Regulation of Anion Exchanger SLC26A6
阴离子交换剂SLC26A6的调节机制
基本信息
- 批准号:8032670
- 负责人:
- 金额:$ 5.4万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-03-15 至 2012-02-29
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAnionsApicalCell LineCellsChimera organismComplement component C1sCyclic AMP-Dependent Protein KinasesCytosolEmployee StrikesEpithelialFormatesGoalsHandHomeostasisHybridsIsoenzymesKidneyMammalian CellMediatingMembraneMethodsMolecularMusNephronsOocytesOxalatesPathway interactionsPeptidesPhosphotransferasesPrecipitationPrincipal InvestigatorProtein IsoformsProtein-Serine-Threonine KinasesProteinsRegulationRetrievalRoleSignal PathwaySpecificitySurfaceTestingUrineXenopus oocyteabsorptionapical membranebaseextracellularinhibitor/antagonistprogramsprotein expressionresearch studyyeast protein
项目摘要
DESCRIPTION (provided by applicant):
The bulk of filtered CI is reabsorbed in the proximal tubule by passive and active pathways. SLC26A6 has recently emerged as the likely key transporter that accounts for reabsorption of this active component, and thus contributes significantly to proximal tubule NaCI absorption and overall renal NaCI and extracellular volume homeostasis. The general project goal is to elucidate the molecular mechanisms regulatingSLC26A6. Preliminary studies by the applicant have indicated that activity of SLC26A6 expressed in Xenopus oocytes is significantly suppressed by activation of PKC-delta, which also altered its surface expression, while unaffected by PKA activation. SLC26A6 was also remarkably suppressed (with reduced surface and total protein expression) when WNK4 was co-expressed in oocytes. A closely related anion transporter, Pendrin (SLC26A4), was unaffected by PKC or WNK4.
Based on these findings, the following specific aims will be pursued:1- Confirm that PKC-delta is the PKC isozyme mediating PKC regulation of SLC26A6 by testing the effects of PKC-delta specific peptide activator and inhibitor, and by evaluating whether PKC-delta translocates from cytosol to membrane. Identify the domain(s) of SLC26A6 essential for its regulation by PKC by analysis of SLC26A6-Pendrin chimeric transporters. 2- Confirm the findings in oocytes by assessing the effects of PKC activation on activity and surface localization of the endogenously expressed SLC26A6 in MPT cells (a mouse proximal tubule cell line). Confirm that PKC-delta is also the involved PKC isoform. Confirm any domain (s) that is (are) identified as critical for PKC regulation of SLC26A6 activity in oocytes in these cells. 3- Evaluate whether WNK4 suppressive regulation of SLC26A6 is at a translational or a post-translational level, such as enhanced endocytic retrieval and subsequent targeting for degradation. Identify the domains of SLC26A6 required for its regulation by WNK4 using a similar approach as in Aim 1.4- Use the domains of SLC26A6 mediating its regulation by PKC and WNK4 to identify potential associated proteins by the yeast-2-hybrid method. Confirm the association of identified proteins with SLC26A6 by co-precipitation experiments. Evaluate the functional roles of these proteins in mediating regulation of SLC26A6 by PKC and WNK4.
描述(由申请人提供):
大部分过滤的CI通过被动和主动途径在近端小管中重吸收。SLC 26 A6最近已成为可能的关键转运蛋白,其解释了该活性组分的重吸收,因此显著促进近端小管NaCl吸收和总体肾NaCl和细胞外容量稳态。本研究的总体目标是阐明调控SLC 26 A6的分子机制。申请人的初步研究表明,在爪蟾卵母细胞中表达的SLC 26 A6的活性被PKC-δ的活化显著抑制,这也改变了其表面表达,而不受PKA活化的影响。当WNK 4在卵母细胞中共表达时,SLC 26 A6也被显著抑制(具有减少的表面和总蛋白表达)。一种密切相关的阴离子转运蛋白Pendrin(SLC 26 A4)不受PKC或WNK 4的影响。
基于这些发现,将追求以下具体目标:1-通过测试PKC-δ特异性肽激活剂和抑制剂的作用,并通过评估PKC-δ是否从胞质溶胶易位到膜,确认PKC-δ是介导SLC 26 A6的PKC调节的PKC同工酶。通过分析SLC 26 A6-Pendrin嵌合转运蛋白,确定SLC 26 A6对其受PKC调节所必需的结构域。2-通过评估PKC活化对MPT细胞(小鼠近端小管细胞系)中内源性表达的SLC 26 A6的活性和表面定位的影响,确认卵母细胞中的发现。确认PKC-δ也是参与的PKC亚型。确认这些细胞中卵母细胞中被鉴定为PKC调节SLC 26 A6活性关键的任何结构域。3-评估WNK 4对SLC 26 A6的抑制性调节是否在翻译或翻译后水平,例如增强的内吞回收和随后的降解靶向。使用与目的1.4类似的方法鉴定WNK 4对其调节所需的SLC 26 A6的结构域-使用介导PKC和WNK 4对其调节的SLC 26 A6的结构域通过酵母双杂交方法鉴定潜在的相关蛋白。通过共沉淀实验确认鉴定的蛋白质与SLC 26 A6的缔合。评估这些蛋白质在介导PKC和WNK 4对SLC 26 A6的调节中的功能作用。
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 }}
HATIM A HASSAN其他文献
HATIM A HASSAN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('HATIM A HASSAN', 18)}}的其他基金
Oxalobacter formigenes-derived Factors Impact Hyperoxalemia, Hyperoxaluria, and Related Kidney Stones
产草酸杆菌衍生因素影响高草酸血症、高草酸尿症和相关肾结石
- 批准号:
10614325 - 财政年份:2022
- 资助金额:
$ 5.4万 - 项目类别:
Oxalobacter formigenes-derived Factors Impact Hyperoxalemia, Hyperoxaluria, and Related Kidney Stones
产草酸杆菌衍生因素影响高草酸血症、高草酸尿和相关肾结石
- 批准号:
10661844 - 财政年份:2022
- 资助金额:
$ 5.4万 - 项目类别:
Oxalobacter formigenes-derived Factors Impact Hyperoxalemia, Hyperoxaluria, and Related Kidney Stones
产草酸杆菌衍生因素影响高草酸血症、高草酸尿和相关肾结石
- 批准号:
9888079 - 财政年份:2020
- 资助金额:
$ 5.4万 - 项目类别:
Oxalobacter formigenes-derived Factors Impact Hyperoxalemia, Hyperoxaluria, and Related Kidney Stones
产草酸杆菌衍生因素影响高草酸血症、高草酸尿症和相关肾结石
- 批准号:
10080732 - 财政年份:2020
- 资助金额:
$ 5.4万 - 项目类别:
Calcium Oxalate Kidney Stones: Pathogenesis of Obesity-associated Hyperoxaluria
草酸钙肾结石:肥胖相关高草酸尿症的发病机制
- 批准号:
8673535 - 财政年份:2014
- 资助金额:
$ 5.4万 - 项目类别:
Mechanisms of Regulation of Anion Exchanger SLC26A6
阴离子交换剂SLC26A6的调节机制
- 批准号:
7031526 - 财政年份:2005
- 资助金额:
$ 5.4万 - 项目类别:
Mechanisms of Regulation of Anion Exchanger SLC26A6
阴离子交换剂SLC26A6的调节机制
- 批准号:
7359685 - 财政年份:2005
- 资助金额:
$ 5.4万 - 项目类别:
Mechanisms of Regulation of Anion Exchanger SLC26A6
阴离子交换剂SLC26A6的调节机制
- 批准号:
6868573 - 财政年份:2005
- 资助金额:
$ 5.4万 - 项目类别:
Mechanisms of Regulation of Anion Exchanger SLC26A6
阴离子交换剂SLC26A6的调节机制
- 批准号:
7191668 - 财政年份:2005
- 资助金额:
$ 5.4万 - 项目类别:
Mechanisms of Regulation of Anion Exchanger SLC26A6
阴离子交换剂SLC26A6的调节机制
- 批准号:
7755525 - 财政年份:2005
- 资助金额:
$ 5.4万 - 项目类别:
相似海外基金
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 5.4万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
- 批准号:
484000 - 财政年份:2023
- 资助金额:
$ 5.4万 - 项目类别:
Operating Grants