The human discs large protein 1 interacts with and maintains connexin 43 at the plasma membrane in keratinocytes.
The human discs large protein 1 interacts with and maintains connexin 43 at the plasma membrane in keratinocytes.
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DOI：
10.1242/jcs.259984
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发表时间：
2023-06-01
影响因子：
4
通讯作者：
中科院分区：
文献类型：
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作者：
缝隙连接通道由连接蛋白组成，允许细胞间的直接通讯。间隙连接蛋白43(Cx43；又称GJA1)广泛表达于包括表皮在内的组织中。在之前对人乳头状瘤病毒阳性的宫颈上皮性肿瘤细胞的研究中，我们发现Cx43是大果蝇盘人同源物(Dlg1；也称为SAP97)的结合伙伴。Dlg1是膜相关鸟苷酸激酶(Maguk)支架蛋白家族中的一员，它控制细胞的形状和极性。在这里，我们发现在体外未感染的角质形成细胞中，Cx43也与Dlg1相互作用，在体内，在正常人的表皮中，Cx43也与角质形成细胞、真皮细胞和脂肪细胞相互作用。角质形成细胞中Dlg1的缺失不会改变Cx43的转录，但与Cx43蛋白水平的降低有关。角质形成细胞中Dlg1水平的降低导致质膜上Cx43的减少，伴随而来的是缝隙连接细胞间通讯的减少和Cx43向高尔基体间的重新定位。我们的数据提示Dlg1在角质形成细胞的质膜上维持Cx43的关键作用。摘要：盘状大蛋白1(Dlg1)与角质形成细胞中的缝隙连接蛋白43(Cx43)相互作用。Dlg1缺失导致Cx43水平降低，细胞间通讯减少。Dlg1可能将Cx43维持在质膜上。
Gap junction channels, composed of connexins, allow direct cell-to-cell communication. Connexin 43 (Cx43; also known as GJA1) is widely expressed in tissues, including the epidermis. In a previous study of human papillomavirus-positive cervical epithelial tumour cells, we identified Cx43 as a binding partner of the human homologue of Drosophila Discs large (Dlg1; also known as SAP97). Dlg1 is a member of the membrane associated-guanylate kinase (MAGUK) scaffolding protein family, which is known to control cell shape and polarity. Here, we show that Cx43 also interacts with Dlg1 in uninfected keratinocytes in vitro and in keratinocytes, dermal cells and adipocytes in normal human epidermis in vivo. Depletion of Dlg1 in keratinocytes did not alter Cx43 transcription but was associated with a reduction in Cx43 protein levels. Reduced Dlg1 levels in keratinocytes resulted in a reduction in Cx43 at the plasma membrane with a concomitant reduction in gap junctional intercellular communication and relocation of Cx43 to the Golgi compartment. Our data suggest a key role for Dlg1 in maintaining Cx43 at the plasma membrane in keratinocytes. Summary: Discs large protein 1 (Dlg1) interacts with the gap junction protein connexin 43 (Cx43) in keratinocytes. Dlg1 depletion leads to low Cx43 levels and reduced intercellular communication. Dlg1 might maintain Cx43 at the plasma membrane.
影响因子：
2.5
作者：
Rivera, Charlene;Yamben, Idella F.;Shatadal, Shalini;Waldof, Malinda;Robinson, Michael L.;Griep, Anne E.
通讯作者：
Griep, Anne E.