哺乳动物Sar1a和Sar1b相似物体在体内的功能重叠
Vi T Tang1,2, Jie Xiang2, Zhimin Chen2
1Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109.
概括
哺乳动物SAR1A和SAR1B蛋白对于细胞内运输至关重要. 在小鼠身上进行的遗传研究显示,这些SAR1对应物具有重叠的功能,这表明SAR1A的上调可以治疗SAR1B的缺乏.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 带有信号或跨膜域的蛋白质进入内质网膜 (ER) 的分泌途径.
- 从ER到戈尔吉装置的传输依赖于COPII囊泡,由SAR1蛋白启动.
- 哺乳动物拥有两种SAR1对应物,SAR1A和SAR1B,具有很高的序列相同性,但功能重叠不明.
研究的目的:
- 为了研究SAR1A和SAR1B对应物之间的体内功能关系.
- 为了确定SAR1A和SAR1B是否在分泌途径中具有不同的或重叠的作用.
- 为了探索SAR1B缺乏症的治疗潜力.
主要方法:
- 在小鼠中Sar1a的遗传失活化.
- 对完全缺乏Sar1b的小鼠进行分析.
- 产生肝细胞特异的Sar1b删除模型.
- 工程小鼠使用 Sar1a 编码序列取代 Sar1b 位点.
主要成果:
- Sar1a无活化导致胚胎发育中期死亡;Sar1b缺乏导致围产死亡.
- 肝细胞特异性的Sar1b删除导致低胆固醇血清,由SAR1A或SAR1B过度表达而挽救.
- 具有Sar1a替代Sar1b的小鼠是可行的,并且在表型上正常,表明功能重叠.
结论:
- 在小鼠中,SAR1A和SAR1B对应物呈现出完全或几乎完全的功能重叠.
- 这些发现表明,SAR1A可以补偿SAR1B的损失.
- 提升SAR1A的调节为人类SAR1B缺乏症 (基洛米克龙保留病) 提供了潜在的治疗策略.
更多相关视频
11:02Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
Published on: May 27, 2016
8.1K
08:01Identification of Homologous Recombination Events in Mouse Embryonic Stem Cells Using Southern Blotting and Polymerase Chain Reaction
Published on: November 20, 2018
9.3K
相关概念视频
Gene Duplication and Divergence
6.1K
The seminal work of Ohno in 1970 popularized the idea of gene duplication and divergence. DNA sequence comparison studies reveal that a large portion of the genes in bacteria, archaebacteria, and eukaryotes was generated by gene duplication and divergence, indicating its critical role in evolution.
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
The duplicated copies of the gene are called Paralogs. Paralogs with similar sequences and functions form a gene family. Across several species, a large number of gene families are...
6.1K
Synteny and Evolution
3.3K
John H. Renwick first coined the term “synteny” in 1971, which refers to the genes present on the same chromosomes, even if they are not genetically linked. The species with common ancestry tend to show conserved syntenic regions. Therefore, the concept of synteny is nowadays used to describe the evolutionary relationship between species.
Around 80 million years ago, the human and mice lineages diverged from the common ancestor. During the course of evolution, the ancestral...
Around 80 million years ago, the human and mice lineages diverged from the common ancestor. During the course of evolution, the ancestral...
3.3K
Gene Families
8.8K
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
8.8K
Coat Assembly and GTPases
3.5K
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
Multi-species Conserved Sequences
3.9K
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
3.9K
Protein Complexes with Interchangeable Parts
2.5K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.5K
