Distinct and Cooperative Functions for the Protocadherin-α, -β and -γ Clusters in Neuronal Survival and Axon Targeting.
Distinct and Cooperative Functions for the Protocadherin-α, -β and -γ Clusters in Neuronal Survival and Axon Targeting.
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DOI：
10.3389/fnmol.2016.00155
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发表时间：
2016
影响因子：
4.8
通讯作者：
Yagi T
中科院分区：
文献类型：
--
作者：
Hasegawa S;Kumagai M;Hagihara M;Nishimaru H;Hirano K;Kaneko R;Okayama A;Hirayama T;Sanbo M;Hirabayashi M;Watanabe M;Hirabayashi T;Yagi T
原钙粘附素(Pcdh)基因簇分为Pcdhα、Pcdhβ和Pcdhγ簇。对小鼠的基因中断分析揭示了Pcdhα和Pcdhγ簇的体内功能。然而，所有的Pcdh蛋白亚型都形成组合的顺式-异型二聚体，并进入反式亲和性相互作用。在这里，我们通过产生6个簇缺失突变体(Δα，Δβ，Δγ，Δαβ，Δβγ和Δαβγ)并比较它们的表型来研究PcdH簇中的不同和合作功能：Δα，Δβ、和Δαβ突变体是活的和可育的；Δγ突变体存活不到12小时；Δβγ和Δαβγ突变体在出生后不久死亡。Pcdhα、Pcdhβ和Pcdhγ簇在嗅轴突靶向和脊髓神经元存活中单独和协同发挥着重要作用。神经退行性变在Δαβγ突变体中最为严重，表明Pcdhα和Pcdhβ对神经元的存活具有协同作用。Pcdhα、Pcdhβ和Pcdhγ簇在嗅轴突靶向和神经元存活中具有共同的作用，尽管程度不同。
The clustered protocadherin (Pcdh) genes are divided into the Pcdhα, Pcdhβ, and Pcdhγ clusters. Gene-disruption analyses in mice have revealed the in vivo functions of the Pcdhα and Pcdhγ clusters. However, all Pcdh protein isoforms form combinatorial cis-hetero dimers and enter trans-homophilic interactions. Here we addressed distinct and cooperative functions in the Pcdh clusters by generating six cluster-deletion mutants (Δα, Δβ, Δγ, Δαβ, Δβγ, and Δαβγ) and comparing their phenotypes: Δα, Δβ, and Δαβ mutants were viable and fertile; Δγ mutants lived less than 12 h; and Δβγ and Δαβγ mutants died shortly after birth. The Pcdhα, Pcdhβ, and Pcdhγ clusters were individually and cooperatively important in olfactory-axon targeting and spinal-cord neuron survival. Neurodegeneration was most severe in Δαβγ mutants, indicating that Pcdhα and Pcdhβ function cooperatively for neuronal survival. The Pcdhα, Pcdhβ, and Pcdhγ clusters share roles in olfactory-axon targeting and neuronal survival, although to different degrees.
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影响因子：
4.8
作者：
Hirano K;Kaneko R;Izawa T;Kawaguchi M;Kitsukawa T;Yagi T
通讯作者：
Yagi T
影响因子：
3.4
作者：
Fukuda, Emi;Hamada, Shun;Yagi, Takeshi
通讯作者：
Yagi, Takeshi
影响因子：
7
作者：
Han, Meng-Hsuan;Lin, Chengyi;Wang, Xiaozhong
通讯作者：
Wang, Xiaozhong
影响因子：
16.2
作者：
Chen WV;Alvarez FJ;Lefebvre JL;Friedman B;Nwakeze C;Geiman E;Smith C;Thu CA;Tapia JC;Tasic B;Sanes JR;Maniatis T
通讯作者：
Maniatis T
影响因子：
16.2
作者：
Goodman KM;Rubinstein R;Thu CA;Bahna F;Mannepalli S;Ahlsén G;Rittenhouse C;Maniatis T;Honig B;Shapiro L
通讯作者：
Shapiro L