Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases
Neuronal RA175/SynCAM1 isoforms are processed by tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases
复制标题
DOI：
10.1016/j.neulet.2008.08.023
复制
发表时间：
2008-10
影响因子：
2.5
通讯作者：
Y. Tanabe;T. Kasahara;T. Momoi;E. Fujita
中科院分区：
文献类型：
--
作者：
Y. Tanabe;T. Kasahara;T. Momoi;E. Fujita
RA 175/SynCAM 1是免疫球蛋白超家族4（Igsf 4;最近命名为Cadm 1）的成员，是参与功能性突触形成的细胞粘附分子。关于RA 175/SynCAM 1介导的突触形成和可塑性的调节知之甚少。神经元表达两种主要亚型，包含外显子7-8a-8b-9和外显子7-8b-9。我们发现，这些异构体内处理的11个氨基酸序列，外显子8b编码，跨膜结构域附近。TNF-α蛋白酶抑制剂-1（TAPI-1）阻断RA 175/SynCAM 1（exons 7-8a-8b-9）的加工。此外，TAPI-1增加突触体素的数量和RA 175/SynCAM 1共定位在神经元树突上。非切割的RA 175/SynCAM 1位于突触和膜结合，在树突的非突触区域检测到切割的片段。这些结果表明，肿瘤坏死因子-α-转换酶（TACE）/ADAM 17样蛋白酶在突触形成中发挥作用，通过处理位于非突触区域的过量RA 175/SynCAM 1产生特定的神经元连接。
RA175/SynCAM1, a member of immunoglobulin superfamily 4 (Igsf4; recently named Cadm1), is a cell adhesion molecule involved in the formation of a functional synapse. Little is known about the modulation of RA175/SynCAM1-mediated synaptic formation and plasticity. Neurons express two major isoforms containing exons 7–8a–8b–9 and exons 7–8b–9. We found that these isoforms were processed within an 11-amino acid sequence, encoded by exon 8b, near the transmembrane domain. TNF-α protease inhibitor-1 (TAPI-1) blocked the processing of RA175/SynCAM1 (exons 7–8a–8b–9). Furthermore, TAPI-1 increased the number of synaptophysin and RA175/SynCAM1 colocalization on the dendrites of neurons. Non-cleaved RA175/SynCAM1 was located at the synapse and membrane-bound, cleaved fragments were detected at the non-synaptic region of dendrites. These results suggest that tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM17-like proteases play a role in synaptic formation to generate specific neuronal connections by processing the excess amount of RA175/SynCAM1 located in the non-synaptic region.