粘合连接
内吞循环
拉布
细胞生物学
生物
紧密连接
肠道通透性
钙粘蛋白
GTP酶
免疫学
内吞作用
生物化学
细胞
作者
Jing Zhang,Zongyan Jiang,Changling Chen,Longfeng Yao,Ziwei Gao,Zihang Cheng,Yanling Yan,Hang Liu,Anbing Shi
出处
期刊:Nature Aging
日期:2023-08-28
卷期号:3 (9): 1107-1127
被引量:7
标识
DOI:10.1038/s43587-023-00475-1
摘要
The age-related decline in the ability of the intestinal barrier to maintain selective permeability can lead to various physiological disturbances. Adherens junctions play a vital role in regulating intestinal permeability, and their proper assembly is contingent upon endocytic recycling. However, how aging affects the recycling efficiency and, consequently, the integrity of adherens junctions remains unclear. Here we show that RAB-10/Rab10 functionality is reduced during senescence, leading to impaired adherens junctions in the Caenorhabditis elegans intestine. Mechanistic analysis reveals that SDPN-1/PACSINs is upregulated in aging animals, suppressing RAB-10 activation by competing with DENN-4/GEF. Consistently, SDPN-1 knockdown alleviates age-related abnormalities in adherens junction integrity and intestinal barrier permeability. Of note, the inhibitory effect of SDPN-1 on RAB-10 requires KGB-1/JUN kinase, which presumably enhances the potency of SDPN-1 by altering its oligomerization state. Together, by examining age-associated changes in endocytic recycling, our study sheds light on how aging can impact intestinal barrier permeability.
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