Autophagic degradation of claudin‐5 mediated by its binding to a Clostridium perfringens enterotoxin fragment modulates endothelial barrier permeability
Autophagic degradation of claudin‐5 mediated by its binding to a Clostridium perfringens enterotoxin fragment modulates endothelial barrier permeability
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DOI：
10.1002/1873-3468.14315
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发表时间：
2022-02
期刊：
影响因子：
3.5
通讯作者：
Panpan Lin;Rongbang Tan;Ping Yu;Yanyu Li;Yuqian Mo;Wen Li;Jingjing Zhang
中科院分区：
文献类型：
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作者：
Panpan Lin;Rongbang Tan;Ping Yu;Yanyu Li;Yuqian Mo;Wen Li;Jingjing Zhang
The blood‐brain barrier (BBB) protects the central nervous system (CNS) from harmful elements, while it also restricts efficient drug delivery into the CNS. Previously, we generated a mutated fragment of Clostridium perfringens enterotoxin (cCPEYWSH) which specifically binds to the endothelial tight junction protein claudin‐5. Here, we explore the mechanisms regulating the dynamics of membranous claudin‐5 and BBB permeability. Following cCPEYWSH binding to claudin‐5, caveolin‐1 mediates the redistribution of claudin‐5 to the cytosol. This abnormal cytosolic aggregation triggers the autophagic degradation of claudin‐5, leading to an increase in BBB permeability. Enhancement or inhibition of autophagy accelerates or inhibits the degradation of cytosolic claudin‐5, respectively. Our findings may pave the way for improving BBB permeability for drug delivery.
