Functions of Family with Sequence Similarity 20 - Member C (FAM20C) andMember A (FAM20A) in Amelogenesis and Dentinogenesis

序列相似性家族20-成员C (FAM20C)和成员A (FAM20A)在釉质发生和牙本质发生中的功能

基本信息

  • 批准号:
    10263267
  • 负责人:
  • 金额:
    $ 41.14万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-14 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Phosphorylation is essential for the phosphorylated proteins to exert their functions in regulating the relevant biological processes. Recent studies have demonstrated that a protein kinase known as “FAM20C” (Family with sequence similarity 20 – member C), together with its paralog named “FAM20A”, plays key and non-redundant functions in phosphorylating serine residues within the Ser-x-Glu/pSer motifs of the secretory proteins, including enamel and dentin matrix proteins that are essential to amelogenesis and dentinogenesis. Although studies have confirmed that FAM20C resides in the Golgi apparatus, it is unclear as to how FAM20C, which does not possess a transmembrane domain, is retained in this organelle to exert its kinase function. While in vitro studies suggest that FAM20A may enhance the kinase activity of FAM20C, whether such functional interaction occurs in ameloblasts and odontoblasts in vivo remains to be determined; FAM20A mutations in humans or its inactivation in mice only affect enamel formation but have no pathological effect on dentin formation, whereas loss of FAM20C function leads to both enamel and dentin defects. The goals of this project are to determine 1) the molecular mechanisms that govern the Golgi-retention of FAM20C, and 2) how FAM20C interacts with FAM20A during amelogenesis and dentinogenesis. Preliminary studies have shown that 1) a FAM20C-related supramolecular complex was present in the cell extract but not in the culture medium when FAM20C was expressed in the transfected cells; 2) a similar large FAM20C-related protein band was also found in the total proteins extracted from the enamel organ (containing ameloblasts) and dental pulp (containing odontoblasts) of mouse teeth; 3) Fam20a-deficient mice developed enamel defects, but had no dentin abnormalities, whereas Fam20c-deficient mice had both enamel and dentin defects; 4) Fam20a-deficient mice had a dramatic reduction in the expression levels of genes encoding the enamel matrix proteins, but showed no expression changes in the genes encoding the major dentin matrix proteins; and 5) Fam20a deletion reduced the level of FAM20C protein in ameloblasts and odontoblasts. These findings lead to the hypothesis that FAM20C forms a supramolecular complex, through which this kinase is retained within the Golgi apparatus, and that FAM20A broadens the substrate spectrum of FAM20C and is required for the proper phosphorylation of the hydrophobic enamel matrix proteins. Two Aims are proposed to test this novel hypothesis: Aim 1 – to determine the mechanisms that govern the Golgi-retention of FAM20C in ameloblasts and odontoblasts. Aim 2 – to determine the functions of FAM20A and FAM20C in ameloblasts and odontoblasts. Successful completion of the proposed work will not only elucidate the molecular mechanisms by which FAM20C and FAM20A function in the phosphorylation of enamel and dentin matrix proteins, but may also provide clues for the development of therapeutic strategies for the clinical management of diseases caused by the FAM20C and FAM20A mutations.
项目总结

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 }}

Yongbo Lu其他文献

Yongbo Lu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('Yongbo Lu', 18)}}的其他基金

Functions of Family with Sequence Similarity 20 - Member C (FAM20C) and Member A (FAM20A) in Amelogenesis and Dentinogenesis
序列相似性家族 20 - 成员 C (FAM20C) 和成员 A (FAM20A) 在釉质形成和牙本质形成中的功能
  • 批准号:
    10094771
  • 财政年份:
    2020
  • 资助金额:
    $ 41.14万
  • 项目类别:
Functions of Family with Sequence Similarity 20 - Member C (FAM20C) andMember A (FAM20A) in Amelogenesis and Dentinogenesis
序列相似性家族20-成员C (FAM20C)和成员A (FAM20A)在釉质发生和牙本质发生中的功能
  • 批准号:
    10685371
  • 财政年份:
    2020
  • 资助金额:
    $ 41.14万
  • 项目类别:
Functions of Family with Sequence Similarity 20 - Member C (FAM20C) andMember A (FAM20A) in Amelogenesis and Dentinogenesis
序列相似性家族20-成员C (FAM20C)和成员A (FAM20A)在釉质发生和牙本质发生中的功能
  • 批准号:
    10467039
  • 财政年份:
    2020
  • 资助金额:
    $ 41.14万
  • 项目类别:
Dentin Sialophosphoprotein (DSPP) and Unfolded Protein Response (UPR) in Dentinogenesis Imperfecta (DGI) and Odontoblast Function
牙本质唾液酸磷蛋白 (DSPP) 和未折叠蛋白反应 (UPR) 在牙本质发育不全 (DGI) 和成牙本质细胞功能中的作用
  • 批准号:
    9752510
  • 财政年份:
    2018
  • 资助金额:
    $ 41.14万
  • 项目类别:
Dentin Sialophosphoprotein (DSPP) and Unfolded Protein Response (UPR) in Dentinogenesis Imperfecta (DGI) and Odontoblast Function
牙本质唾液酸磷蛋白 (DSPP) 和未折叠蛋白反应 (UPR) 在牙本质发育不全 (DGI) 和成牙本质细胞功能中的作用
  • 批准号:
    10190893
  • 财政年份:
    2018
  • 资助金额:
    $ 41.14万
  • 项目类别:
Dentin Sialophosphoprotein (DSPP) and Unfolded Protein Response (UPR) in Dentinogenesis Imperfecta (DGI) and Odontoblast Function
牙本质唾液酸磷蛋白 (DSPP) 和未折叠蛋白反应 (UPR) 在牙本质发育不全 (DGI) 和成牙本质细胞功能中的作用
  • 批准号:
    10404027
  • 财政年份:
    2018
  • 资助金额:
    $ 41.14万
  • 项目类别:
Identification and Function of nuDMP1 in Odontoblast Differentiation
nuDMP1在成牙本质细胞分化中的鉴定及其功能
  • 批准号:
    9038177
  • 财政年份:
    2013
  • 资助金额:
    $ 41.14万
  • 项目类别:
Identification and Function of nuDMP1 in Odontoblast Differentiation
nuDMP1在成牙本质细胞分化中的鉴定及其功能
  • 批准号:
    8483222
  • 财政年份:
    2013
  • 资助金额:
    $ 41.14万
  • 项目类别:
Identification and Function of nuDMP1 in Odontoblast Differentiation
nuDMP1在成牙本质细胞分化中的鉴定及其功能
  • 批准号:
    8637971
  • 财政年份:
    2013
  • 资助金额:
    $ 41.14万
  • 项目类别:
Studies of the Roles of Twist1 and E12 in Tooth Morphogenesis
Twist1 和 E12 在牙齿形态发生中的作用研究
  • 批准号:
    8328601
  • 财政年份:
    2011
  • 资助金额:
    $ 41.14万
  • 项目类别:

相似海外基金

Regulation of the RA-SA cycle in maturation stage ameloblasts by energy metabolic shift
通过能量代谢转变调节成熟期成釉细胞的 RA-SA 循环
  • 批准号:
    22K21021
  • 财政年份:
    2022
  • 资助金额:
    $ 41.14万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Elucidation of the regulatory mechanism of ameloblasts by lipid mediators and the etiology due to their destruction.
阐明脂质介质对成釉细胞的调节机制及其破坏的病因学。
  • 批准号:
    21K09832
  • 财政年份:
    2021
  • 资助金额:
    $ 41.14万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Tooth formation using mouse tooth progenitor cells that can fluorescently label odontoblasts and ameloblasts.
使用可以荧光标记成牙本质细胞和成釉细胞的小鼠牙齿祖细胞形成牙齿。
  • 批准号:
    19K10041
  • 财政年份:
    2019
  • 资助金额:
    $ 41.14万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of enamel matrix protein secretion in ameloblasts
成釉细胞釉质基质蛋白分泌的调节
  • 批准号:
    10192703
  • 财政年份:
    2017
  • 资助金额:
    $ 41.14万
  • 项目类别:
The role of non-muscle myosin II for the niche formation of dental epithelial stem cells and the movement of ameloblasts
非肌肉肌球蛋白II对牙上皮干细胞生态位形成和成釉细胞运动的作用
  • 批准号:
    16K11453
  • 财政年份:
    2016
  • 资助金额:
    $ 41.14万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Relationship between blood vessels in stellate reticulum and microenvironmental change in ameloblasts differentiation
星状网血管与成釉细胞分化微环境变化的关系
  • 批准号:
    26462794
  • 财政年份:
    2014
  • 资助金额:
    $ 41.14万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Expression profiling of the protease Gm5771 in ameloblasts
成釉细胞中蛋白酶 Gm5771 的表达谱
  • 批准号:
    465872-2014
  • 财政年份:
    2014
  • 资助金额:
    $ 41.14万
  • 项目类别:
    University Undergraduate Student Research Awards
The novel exploration of the factors for maintaining the function of ameloblasts and stratum intermedium during mouse enamel formation
小鼠牙釉质形成过程中成釉细胞和中间层功能维持因素的新探索
  • 批准号:
    25861741
  • 财政年份:
    2013
  • 资助金额:
    $ 41.14万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Role of ameloblastin for ameloblasts and enamel formation
成釉细胞蛋白对成釉细胞和牙釉质形成的作用
  • 批准号:
    8354357
  • 财政年份:
    2012
  • 资助金额:
    $ 41.14万
  • 项目类别:
Role of ameloblastin for ameloblasts and enamel formation
成釉细胞蛋白对成釉细胞和牙釉质形成的作用
  • 批准号:
    8699033
  • 财政年份:
    2012
  • 资助金额:
    $ 41.14万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了