Sirnes Solveig, Leithe Edward, Rivedal Edgar
Department of Cancer Prevention, The Norwegian Radium Hospital, Rikshospitalet, Montebello, Oslo, Norway.
Biochem Biophys Res Commun. 2008 Sep 5;373(4):597-601. doi: 10.1016/j.bbrc.2008.06.095. Epub 2008 Jul 2.
Gap junctions are plasma membrane domains containing channels that directly connect the cytosols of neighbouring cells. Gap junction channels are made of a family of transmembrane proteins called connexins, of which the best studied is Connexin43 (Cx43). MAP kinase-induced phosphorylation of Cx43 has previously been shown to cause inhibition of gap junction channel permeability and increased Cx43 endocytosis. As Cx43 assembles into gap junction plaques, Cx43 acquires detergent resistance. Here we report that the detergent resistance is lost after activation of MAP kinase. Treatment of IAR20 rat liver epithelial cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) or epidermal growth factor (EGF) caused a rapid increase in the solubility of Cx43 in Triton X-100. This process was mediated by MAP kinase and was initiated at the plasma membrane. The data suggest that loss of the detergent resistance of Cx43 is an early step in TPA- and EGF-induced endocytosis of gap junctions.
间隙连接是质膜结构域，包含直接连接相邻细胞质溶胶的通道。间隙连接通道由一类称为连接蛋白的跨膜蛋白组成，其中研究最深入的是连接蛋白43（Cx43）。先前已表明，丝裂原活化蛋白激酶（MAP激酶）诱导的Cx43磷酸化会导致间隙连接通道通透性受到抑制，并增加Cx43的内吞作用。当Cx43组装成间隙连接斑时，Cx43获得抗去污剂能力。在此我们报告，MAP激酶激活后，抗去污剂能力丧失。用12 - O - 十四烷酰佛波醇13 - 乙酸酯（TPA）或表皮生长因子（EGF）处理IAR20大鼠肝上皮细胞，会导致Cx43在Triton X - 100中的溶解度迅速增加。这一过程由MAP激酶介导，始于质膜。数据表明，Cx43抗去污剂能力的丧失是TPA和EGF诱导间隙连接内吞作用的早期步骤。
