Abstract：
LMNA gene mutation can cause muscular dystrophy, and post-translational modification plays a critical role in regulating its function. Here, we identify that lamin A is palmitoylated at cysteine 522, 588, and 591 residues, which are reversely catalyzed by palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) and depalmitoylase α/β hydrolase domain 7 (ABHD7). Furthermore, the metabolite lactate promotes palmitoylation of lamin A by inhibiting the interaction between it and ABHD7. Interestingly, low-level palmitoylation of lamin A promotes, whereas high-level palmitoylation of lamin A inhibits, murine myoblast differentiation. Together, these observations suggest that ABHD7-mediated depalmitoylation of lamin A controls myoblast differentiation.
摘要：
LMNA基因突变可引起肌营养不良,翻译后修饰在调节其功能中起着关键作用。这里,我们确定层粘连蛋白A在半胱氨酸522、588和591个残基处被棕榈酰化，它们由棕榈酰基转移酶锌指DHHC型棕榈酰基转移酶5（ZDHHC5）和脱棕榈酰基转移酶α/β水解酶结构域7（ABHD7）反向催化。此外，代谢产物乳酸通过抑制层粘连蛋白A与ABHD7之间的相互作用来促进层粘连蛋白A的棕榈酰化。有趣的是,层粘连蛋白A的低水平棕榈酰化促进，而高水平的层粘连蛋白A的棕榈酰化抑制，小鼠成肌细胞分化。一起,这些观察结果表明，ABHD7介导的层粘连蛋白A的脱棕榈酰化控制成肌细胞分化。
