DHHC17 Palmitoylates ClipR-59 and Modulates ClipR-59 Association with the Plasma Membrane
DHHC17 Palmitoylates ClipR-59 and Modulates ClipR-59 Association with the Plasma Membrane
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DOI：
10.1128/mcb.00527-13
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发表时间：
2013-11-01
影响因子：
5.3
通讯作者：
Du, Keyong
中科院分区：
文献类型：
--
作者：
Ren, Wenying;Sun, Yingmin;Du, Keyong
ClipR-59与Akt相互作用并以质膜缔合依赖性方式调节Akt区室化和Glut 4膜运输。ClipR-59与质膜的结合是由ClipR-59在Cys 534和Cys 535处的棕榈酰化介导的。为了了解ClipR-59棕榈酰化的调节，我们检查了所有已知的哺乳动物DHHC棕榈酰转移酶促进ClipR-59棕榈酰化的能力。我们发现，在23种哺乳动物DHHC棕榈酰转移酶中，DHHC 17是主要的ClipR-59棕榈酰转移酶，这一事实证明，DHHC 17与ClipR-59和棕榈酰化ClipR-59在Cys 534和Cys 535处相互作用。通过棕榈酰化ClipR-59，DHHC 17直接调节ClipR-59质膜结合，因为DHHC 17的异位表达增加，而DHHC 17的沉默降低了与质膜结合的ClipR-59的水平。我们还研究了DHHC 17在Akt信号传导中的作用，发现DHHC 17在3 T3-L1脂肪细胞中的沉默降低了Akt以及质膜上的ClipR-59的水平，并损害了胰岛素依赖性Glut 4膜转位。我们认为DHHC 17是一种ClipR-59棕榈酰转移酶，可调节ClipR-59质膜结合，从而调节脂肪细胞中的Akt信号传导和Glut 4膜转位。
ClipR-59 interacts with Akt and regulates Akt compartmentalization and Glut4 membrane trafficking in a plasma membrane association-dependent manner. The association of ClipR-59 with plasma membrane is mediated by ClipR-59 palmitoylation at Cys534 and Cys535. To understand the regulation of ClipR-59 palmitoylation, we have examined all known mammalian DHHC palmitoyltransferases with respect to their ability to promote ClipR-59 palmitoylation. We found that, among 23 mammalian DHHC palmitoyltransferases, DHHC17 is the major ClipR-59 palmitoyltransferase, as evidenced by the fact that DHHC17 interacted with ClipR-59 and palmitoylated ClipR-59 at Cys534 and Cys535. By palmitoylating ClipR-59, DHHC17 directly regulates ClipR-59 plasma membrane association, as ectopic expression of DHHC17 increased whereas silencing of DHHC17 reduced the levels of ClipR-59 associated with plasma membrane. We have also examined the role of DHHC17 in Akt signaling and found that silencing of DHHC17 in 3T3-L1 adipocytes decreased the levels of Akt as well as ClipR-59 on the plasma membrane and impaired insulin-dependent Glut4 membrane translocation. We suggest that DHHC17 is a ClipR-59 palmitoyltransferase that modulates ClipR-59 plasma membrane binding, thereby regulating Akt signaling and Glut4 membrane translocation in adipocytes.