期刊
AUTOPHAGY
卷 16, 期 10, 页码 1753-1770出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1707488
关键词
Autophagy; KAT2A; GCN5; microtubule; TUBA; alpha-tubulin; VSMCs
类别
资金
- American Heart Association [6GRANT29590003]
- NIH [HL128014, HL132500, HL137371, HL142287]
- NIH [NHLBI] [HL079584, HL080499, HL089920, HL110488, CA213022, AG047776]
Macroautophagy/autophagy, a fundamental process for degradation of macromolecules and organelles, occurs constitutively at a basal level and is upregulated in response to stress. Whether autophagy regulates protein acetylation and microtubule stability in vascular smooth muscle cells (VSMCs) migration, however, remains unknown. Here, we demonstrate that the histone acetyltransferase KAT2A/GCN5 (lysine acetyltransferase 2) binds directly to the autophagosome protein MAP1LC3/LC3 (microtubule associated protein 1 light chain 3) via a conserved LC3-interacting region (LIR) domain. This interaction is required for KAT2A sequestration in autophagosomes and degradation by lysosomal acid hydrolases. Suppression of autophagy results in KAT2A accumulation. KAT2A functions as an acetyltransferase to increase TUBA/alpha-tubulin acetylation, promote microtubule polymerization and stability, ultimately inhibiting directional cell migration. Our findings indicate that deacetylation of TUBA and perturbation of microtubule stability via selective autophagic degradation of KAT2A are essential for autophagy-promoting VSMC migration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据