Understanding cadherin EGF LAG seven-pass G-type receptors.
Understanding cadherin EGF LAG seven-pass G-type receptors.
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DOI：
10.1111/jnc.12955
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发表时间：
2014-12
影响因子：
4.7
通讯作者：
Sun JP
中科院分区：
文献类型：
--
作者：
Wang XJ;Zhang DL;Xu ZG;Ma ML;Wang WB;Li LL;Han XL;Huo Y;Yu X;Sun JP
钙粘蛋白EGF LAG七通道G型受体（CELSRs）是粘附G蛋白偶联受体（GPCRs）的一个特殊亚类，在胚胎发育过程中参与神经/内分泌细胞分化、血管瓣膜形成和平面细胞极性控制等生物学过程。CELSR家族的所有三个成员（CELSR 1 -3）都具有形成嗜同性相互作用的大胞外结构域，并包含超过2，000个氨基酸。CELSR的胞外域或其他基因位置的突变与人类神经管缺陷（NTD）和其他疾病相关。细胞基因敲除（KO）动物具有许多发育缺陷。因此，CELSR成员的特异性激动剂或拮抗剂可能具有治疗潜力。尽管关于CELSRs的功能和生化特性已经取得了重大进展，但我们对这些受体的了解仍然缺乏，特别是考虑到它们广泛分布，但在有限数量的组织中具有很少的特征功能。CELSRs的动态激活和失活以及嗜同性相互作用之外的内源性配体的存在仍然难以捉摸，这些受体的调控机制和下游信号传导也是如此。鉴于这一动机，未来使用更先进的细胞生物学或生化工具（如条件性KO小鼠）进行的研究可能会进一步深入了解CELSR功能的机制，为设计新的CELSR靶向治疗试剂奠定基础。
The cadherin EGF LAG seven-pass G-type receptors (CELSRs) are a special subgroup of adhesion G protein-coupled receptors (GPCRs), which are pivotal regulators of many biological processes such as neuronal/endocrine cell differentiation, vessel valve formation and the control of planar cell polarity during embryonic development. All three members of the CELSR family (CELSR1-3) have large ecto-domains that form homophilic interactions and encompass more than 2,000 amino acids. Mutations in the ecto-domain or other gene locations of CELSRs are associated with neural tube defects (NTDs) and other diseases in humans. Celsr knockout (KO) animals have many developmental defects. Therefore, specific agonists or antagonists of CELSR members may have therapeutic potential. Although significant progress has been made regarding the functions and biochemical properties of CELSRs, our knowledge of these receptors is still lacking, especially considering that they are broadly distributed but have few characterized functions in a limited number of tissues. The dynamic activation and inactivation of CELSRs and the presence of endogenous ligands beyond homophilic interactions remain elusive, as do the regulatory mechanisms and downstream signaling of these receptors. Given this motivation, future studies with more advanced cell biology or biochemical tools, such as conditional KO mice, may provide further insights into the mechanisms underlying CELSR function, laying the foundation for the design of new CELSR-targeted therapeutic reagents.
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DOI：
10.1523/jneurosci.4508-10.2010
发表时间：
2010-11-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fenstermaker AG;Prasad AA;Bechara A;Adolfs Y;Tissir F;Goffinet A;Zou Y;Pasterkamp RJ
通讯作者：
Pasterkamp RJ
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DOI：
10.1126/science.1244392
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bae BI;Tietjen I;Atabay KD;Evrony GD;Johnson MB;Asare E;Wang PP;Murayama AY;Im K;Lisgo SN;Overman L;Šestan N;Chang BS;Barkovich AJ;Grant PE;Topçu M;Politsky J;Okano H;Piao X;Walsh CA
通讯作者：
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影响因子：
2.5
作者：
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通讯作者：
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影响因子：
11.4
作者：
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通讯作者：
Brunger, Axel T.
影响因子：
2.5
作者：
Arvind, Prathima;Nair, Jiny;Shanker, Jayashree
通讯作者：
Shanker, Jayashree