Department of Anatomy and Division of Brain Korea, Korea University College of Medicine; Anam-Dong, Seoul, South Korea.
Cell Adh Migr. 2011 Mar-Apr;5(2):97-105. doi: 10.4161/cam.5.2.14374. Epub 2011 Mar 1.
The cadherin family is classified into classical cadherins, desmosomal cadherins and protocadherins (PCDHs). Genomic structures distinguish between PCDHs and other cadherins, and between clustered and non-clustered PCDHs. The phylogenetic analysis with full sequences of non-clustered PCDHs enabled them to be further classified into three subgroups: δ1 (PCDH1, PCDH7, PCDH9, PCDH11 and PCDH20), δ2 (PCDH8, PCDH10, PCDH12, PCDH17, PCDH18 and PCDH19) and ε (PCDH15, PCDH16, PCDH21 and MUCDHL). ε-PCDH members except PCDH21 have either higher or lower numbers of cadherin repeats than those of other PCDHs. Non-clustered PCDHs are expressed predominantly in the nervous system and have spatiotemporally diverse expression patterns. Especially, the region-specific expressions of non-clustered PCDHs have been observed in cortical area of early postnatal stage and in caudate putaman and/or hippocampal formation of mature brains, suggesting that non-clustered PCDHs play roles in the circuit formation and maintenance. The non-clustered PCDHs appear to have homophilic/heterophilc cell-cell adhesion properties, and each member has diverse cell signaling partnership distinct from those of other members (PCDH7/TAF1; PCDH8/TAO2β; PCDH10/Nap1; PCDH11/β-catenin; PCDH18/mDab1). Furthermore, each PCDH has several isoforms with differential cytoplasmic sequences, suggesting that one PCDH isoform could activate intracellular signaling differential from other isoforms. These facts suggest that non-clustered PCDHs play roles as a mediator of a regulator of other molecules as well as cell-cell adhesion. Furthermore, some non-clustered PCDHs have been considered to be involved in neuronal diseases such as autism-spectrum disorders, schizophrenia, and female-limited epilepsy and cognitive impairment, suggesting that they play multiple, tightly regulated roles in normal brain function. In addition, some non-clustered PCDHs have been suggested as candidate tumor suppressor genes in several tissues. Although molecular adhesive and regulatory properties of some PCDHs began to be unveiled, the endeavor to understand the molecular mechanism of non-clustered PCDH is still in its infancy and requires future study.
钙黏蛋白家族可分为经典钙黏蛋白、桥粒钙黏蛋白和原钙黏蛋白（PCDHs）。基因组结构将 PCDHs 与其他钙黏蛋白区分开来，也将聚集性和非聚集性 PCDHs 区分开来。非聚集性 PCDHs 的全长序列的系统发生分析将它们进一步分为三个亚组：δ1（PCDH1、PCDH7、PCDH9、PCDH11 和 PCDH20）、δ2（PCDH8、PCDH10、PCDH12、PCDH17、PCDH18 和 PCDH19）和 ε（PCDH15、PCDH16、PCDH21 和 MUCDHL）。除了 PCDH21 之外，ε-PCDH 成员的钙黏蛋白重复数要么比其他 PCDHs 多，要么比其他 PCDHs 少。非聚集性 PCDHs 主要在神经系统中表达，并且具有时空多样化的表达模式。特别是，在早期出生后阶段的皮质区和成熟大脑的尾状核和/或海马结构中观察到非聚集性 PCDHs 的区域特异性表达，表明非聚集性 PCDHs 在回路形成和维持中发挥作用。非聚集性 PCDHs 似乎具有同亲性/异亲性细胞-细胞粘附特性，并且每个成员都与其他成员（PCDH7/TAF1；PCDH8/TAO2β；PCDH10/Nap1；PCDH11/β-catenin；PCDH18/mDab1）具有不同的细胞信号伙伴关系。此外，每个 PCDH 都有几个具有差异细胞质序列的同工型，表明一个 PCDH 同工型可以激活不同于其他同工型的细胞内信号。这些事实表明，非聚集性 PCDHs 作为其他分子的介体和调节剂发挥作用。此外，一些非聚集性 PCDHs 被认为与自闭症谱系障碍、精神分裂症和女性特发性癫痫和认知障碍等神经疾病有关，这表明它们在正常大脑功能中发挥着多种、紧密调节的作用。此外，一些非聚集性 PCDHs 已被认为是几种组织中的候选肿瘤抑制基因。尽管一些 PCDH 的分子粘附和调节特性开始被揭示，但对非聚集性 PCDH 分子机制的研究仍处于起步阶段，需要进一步研究。
