Autophagy: a pathway that contributes to connexin degradation
Autophagy: a pathway that contributes to connexin degradation
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DOI：
10.1242/jcs.073072
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发表时间：
2011-03-15
影响因子：
4
通讯作者：
Berthoud, Viviana M.
中科院分区：
文献类型：
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作者：
Lichtenstein, Alexandra;Minogue, Peter J.;Berthoud, Viviana M.
连接蛋白形成缝隙连接，其功能可以通过降解快速调节，因为它们的半衰期只有几个小时。自噬是一种与多种疾病有关的降解途径，可由细胞应激（如饥饿）诱导。我们研究了自噬参与野生型连接蛋白CX50和CX43以及白内障相关连接蛋白突变体CX50P88S的蛋白水解，CX50P88S形成细胞质积累。我们观察到，细胞质连接蛋白部分（杯形）或完全（环形）封闭的结构包含自噬相关蛋白LC 3。细胞内连接蛋白也与p62共定位，p62是一种可能作为自噬降解的货物受体的蛋白质。饥饿诱导连接蛋白水平下降，这被氯喹（一种溶酶体蛋白酶抑制剂）或自噬相关蛋白Atg5的敲低所阻断。这些结果表明，自噬可以调节野生型连接蛋白的细胞水平，并暗示CX50P88S积累的持续性是由于组成性自噬的降解能力不足。
The function of connexins, which form gap junctions, can be rapidly modulated by degradation, because they have half-lives of only a few hours. Autophagy is a degradation pathway that has been implicated in several diseases and can be induced by cellular stresses such as starvation. We investigated the involvement of autophagy in proteolysis of the wild-type connexins CX50 and CX43, and a cataract-associated connexin mutant, CX50P88S, which forms cytoplasmic accumulations. We observed that cytoplasmic connexins were partially (cup-shaped) or completely (ring-shaped) enclosed by structures containing the autophagy-related protein LC3. Intracellular connexins also colocalized with p62, a protein that might serve as a cargo receptor for autophagic degradation. Starvation induced a decrease in connexin levels that was blocked by treatment with chloroquine, a lysosomal protease inhibitor, or by knockdown of the autophagy-related protein Atg5. These results demonstrate that autophagy can regulate cellular levels of wild-type connexins and imply that the persistence of accumulations of CX50P88S results from insufficient degradation capacity of constitutive autophagy.