프로토cadherins 在哺乳动物神经系统中调解树突性自我回避
Julie L Lefebvre1, Dimitar Kostadinov, Weisheng V Chen
1Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature
|July 31, 2012
概括
聚类原干素 (Pcdhs) 使神经元能够避免自我分支,并区分自我和非自我细胞. 这确保了正确的神经电路的形成和功能.
科学领域:
- 神经科学是一个神经科学.
- 发育生物学 发展生物学
- 分子生物学分子生物学
背景情况:
- 神经元树状树木化是由自我避开的模式,其中来自同一个神经元的分支相互排斥.
- 自我避开确保了神经元的领土的完整覆盖,最大限度地减少差距和重叠.
- 一些表现出自我回避的神经元可以与相同亚型的其他神经元相互作用,表明自我/非自我歧视.
研究的目的:
- 为了研究聚类原cadherin (Pcdhs) 在树突自我回避和自我/非自我歧视中的作用.
- 阐明PCdhs调节神经元线路的分子机制.
主要方法:
- 在小鼠视网膜星爆亚马克林细胞 (SACs) 和小脑Purkinje细胞中对聚合的原始甲林玛 (Pcdhg) 基因进行基因分析.
- 功能性研究涉及基因删除和异形替代,以评估对树突自我回避的影响.
- 在神经元发育过程中研究PCdhg蛋白的细胞自主功能.
主要成果:
- 删除Pcdhg基因破坏了SAC和Purkinje细胞中的树突自我避开.
- Pcdhg蛋白质以细胞自主作用;用单个异形体取代22个Pcdhg蛋白质恢复了自我避开.
- 在所有SAC中表达单个PCdhg异型,可以减少邻近SAC树突之间的相互作用 (异质神经相互作用).
结论:
- 兄弟神经元之间的同性恋Pcdhg相互作用 (同位神经元相互作用) 产生排斥信号,导致树突性自我回避.
- 自我/非自我区分是可以实现的,因为异质神经元相互作用是允许的,除非树突共享一组匹配的PCdhg蛋白.
- 脊椎动物Pcdhs和昆虫Dscam1在神经元自我回避和自我/非自我歧视方面采用了类似的策略,尽管缺乏序列同质性.
相关概念视频
Cadherins in Tissue Organization
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
Structure of Cadherins
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This diversity of cadherins...
Catenins
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the adherens...
Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
Desmosomes
The term desmosome derives from the Greek words "desmo" and "soma" meaning "adhesion bodies." This structure was first observed during the late 1800s and described as small, dense nodules in the epidermis. Desmosomes are button-like structures that help form an interlinked network of intermediate filaments across the cells. These junctions are essential to hold cells together under mechanical stress and to maintain tissue integrity. Desmosomes are multi-protein complexes comprising desmosomal...


