Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules
Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules
复制标题
DOI：
10.1074/jbc.273.5.2808
复制
发表时间：
1998-01-30
影响因子：
4.8
通讯作者：
Harris, AL
中科院分区：
文献类型：
--
作者：
Bevans, CG;Kordel, M;Harris, AL
细胞间连接蛋白通道(缝隙连接通道)长期以来一直被认为是细胞间分子信号的中介，但信号的性质一直不清楚。这项研究表明，天然组织的连接蛋白通道具有选择性通透性，部分基于孔径，区分细胞质第二信使分子。通透性是通过测量含有重组连接蛋白通道的脂质体中示踪剂的选择性损失/保留来评估的。所使用的示踪剂是氚标记的环核苷酸和一系列带有小的不带电荷的荧光部分衍生的低聚半乳糖，数据定义了通过同质连接蛋白-32通道和通过异构体连接蛋白-32/连接蛋白-26通道的不同大小的渗透限，连接蛋白-26有助于缩小孔道，cAMP和cGMP都可以通过同质连接蛋白-32通道渗透。CAMP只通过一小部分异构体通道，令人惊讶的是，cGMP通过异构体通道的比例比cAMP大得多。这些数据表明，连接蛋白通道内的亚型化学计量和/或排列决定了环核苷酸是否可以渗透，以及哪些环核苷酸可以渗透，这是生物信号分子中连接蛋白特异性选择性的第一个证据。
Intercellular connexin channels (gap junction channels) have long been thought to mediate molecular signaling between cells, but the nature of the signaling has been unclear. This study shows that connexin channels from native tissue have selective permeabilities, partially based on pore diameter, that discriminate among cytoplasmic second messenger molecules, Permeability was assessed by measurement of selective loss/retention of tracers from liposomes containing reconstituted connexin channels. The tracers employed were tritiated cyclic nucleotides and a series of oligomaltosaccharides derivatized with a small uncharged fluorescent moiety, The data define different size cut-off limits for permeability through homomeric connexin-32 channels and through heteromeric connexin-32/connexin-26 channels, Connexin-26 contributes to a narrowed pore, Both cAMP and cGMP were permeable through the homomeric connexin-32 channels. cAMP was permeable through only a fraction of the heteromeric channels, Surprisingly, cGMP was permeable through a substantially greater fraction of the heteromeric channels than was cAMP. The data suggest that isoform stoichiometry and/or arrangement within a connexin channel determines whether cyclic nucleotides can permeate, and which ones, This is the first evidence for connexin-specific selectivity among biological signaling molecules.