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首页> 外文期刊>Molecular and Cellular Biology >Combinatorial Expression of α- and γ-Protocadherins Alters Their Presenilin-Dependent Processing
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Combinatorial Expression of α- and γ-Protocadherins Alters Their Presenilin-Dependent Processing

机译：α-和γ-前钙粘着蛋白的组合表达改变了它们早老素依赖性的加工

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摘要

α- and γ-protocadherins (Pcdhs) are type I transmembrane receptors expressed predominantly in the central nervous system and located in part in synapses. They are transcribed from complex genomic loci, giving rise in the mouse to 14 α-Pcdh and 22 γ-Pcdh isoforms consisting of variable domains, each encompassing the extracellular region, the transmembrane region, and part of the intracellular region harboring the α- or γ-Pcdh-specific invariant cytoplasmic domain. Presenilin-dependent intramembrane proteolysis (PS-IP) of γ-Pcdhs and the formation of α/γ-Pcdh heteromers led us to investigate the effects of homo- and heteromer formation on γ- and putative α-Pcdh membrane processing and signaling. We find that upon surface delivery, α-Pcdhs, like γ-Pcdhs, are subject to matrix metallo-protease cleavage followed by PS-IP in neurons. We further demonstrate that the combinatorial expression of α- and γ-Pcdhs modulates the extent of their PS-IP, indicating the formation of α/γ-Pcdh heteromers with an altered susceptibility to processing. Cell-specific expression of α/γ-Pcdh isoforms could thus determine cell and synapse adhesive properties as well as intracellular and nuclear signaling by their soluble cytoplasmic cleavage products, α C-terminal fragment 2 (α-CTF-2) and γ-CTF-2.
机译：α-和γ-procadadherins（Pcdhs）是I型跨膜受体，主要在中枢神经系统中表达，部分位于突触中。它们从复杂的基因组位点转录而来，在小鼠中产生14个α-Pcdh和22个γ-Pcdh亚型，这些亚型由可变域组成，每个域都包含细胞外区域，跨膜区域以及部分具有α-或-α的细胞内区域。 γ-Pcdh特异的恒定胞质结构域。早老素依赖性的γ-Pcdhs膜内蛋白水解（PS-IP）和α/γ-Pcdh杂聚体的形成使我们研究了同质和异聚体形成对γ-和假定的α-Pcdh膜加工和信号传导的影响。我们发现，在表面递送后，α-Pcdhs与γ-Pcdhs一样，会受到基质金属蛋白酶的切割，然后在神经元中被PS-IP切割。我们进一步证明，α-和γ-Pcdhs的组合表达调节其PS-IP的程度，表明形成了具有改变的加工敏感性的α/γ-Pcdh杂聚物。因此，α/γ-Pcdh亚型的细胞特异性表达可通过其可溶性胞质裂解产物，αC-末端片段2（α-CTF-2）和γ-CTF来确定细胞和突触的粘附特性以及细胞内和核信号传导。 -2。

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