Glut4在半胱氨酸223处的棕榈酰化在Glut4膜转运中起关键作用。
Glut4 palmitoylation at Cys223 plays a critical role in Glut4 membrane trafficking.
作者信息
Ren Wenying, Sun Yingmin, Du Keyong
机构信息
Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
出版信息
Biochem Biophys Res Commun. 2015 May 8;460(3):709-14. doi: 10.1016/j.bbrc.2015.03.094. Epub 2015 Mar 27.
Abstract
Recently, we identified Glut4 as a palmitoylated protein in adipocytes. To understand the role of Glut4 palmitoylation in Glut4 membrane trafficking, a process that is essential for maintenance of whole body glucose homeostasis, we have characterized Glut4 palmitoylation. We found that Glut4 is palmitoylated at Cys223 and Glut4 palmitoylation at Cys223 is essential for insulin dependent Glut4 membrane translocation as substitution of Cys223 with a serine residue in Glut4 (C223S Glut4) diminished Glut4 responsiveness to insulin in membrane translocation in both adipocytes and CHO-IR cells. We have examined C223S Glut4 subcellular localization and observed that it was absence from tubular-vesicle structure, where insulin responsive Glut4 vesicles were presented. Together, our studies uncover a novel mechanism under which Glut4 palmitoylation regulates Glut4 sorting to insulin responsive vesicles, thereby insulin-dependent Glut4 membrane translocation.
摘要
最近，我们确定了Glut4是脂肪细胞中的一种棕榈酰化蛋白。为了了解Glut4棕榈酰化在Glut4膜转运中的作用，这一过程对维持全身葡萄糖稳态至关重要，我们对Glut4棕榈酰化进行了表征。我们发现Glut4在半胱氨酸223处被棕榈酰化，并且半胱氨酸223处的Glut4棕榈酰化对于胰岛素依赖的Glut4膜易位至关重要，因为用丝氨酸残基取代Glut4中的半胱氨酸223（C223S Glut4）会降低脂肪细胞和CHO-IR细胞中Glut4在膜易位中对胰岛素的反应性。我们检查了C223S Glut4的亚细胞定位，发现它不存在于管状小泡结构中，而胰岛素反应性Glut4小泡存在于该结构中。总之，我们的研究揭示了一种新机制，即Glut4棕榈酰化调节Glut4分选至胰岛素反应性小泡，从而调节胰岛素依赖的Glut4膜易位。
相似文献
1
Glut4 palmitoylation at Cys223 plays a critical role in Glut4 membrane trafficking.Glut4在半胱氨酸223处的棕榈酰化在Glut4膜转运中起关键作用。
Biochem Biophys Res Commun. 2015 May 8;460(3):709-14. doi: 10.1016/j.bbrc.2015.03.094. Epub 2015 Mar 27.
2
DHHC7 Palmitoylates Glucose Transporter 4 (Glut4) and Regulates Glut4 Membrane Translocation.DHHC7使葡萄糖转运蛋白4（Glut4）发生棕榈酰化并调节Glut4的膜转位。
J Biol Chem. 2017 Feb 17;292(7):2979-2991. doi: 10.1074/jbc.M116.747139. Epub 2017 Jan 5.
3
4
The glucose transporter 4 FQQI motif is necessary for Akt substrate of 160-kilodalton-dependent plasma membrane translocation but not Golgi-localized (gamma)-ear-containing Arf-binding protein-dependent entry into the insulin-responsive storage compartment.葡萄糖转运蛋白4的FQQI基序对于160千道尔顿依赖性质膜转位的Akt底物是必需的，但对于含高尔基体定位的γ耳的Arf结合蛋白依赖性进入胰岛素反应性储存区室不是必需的。
Mol Endocrinol. 2007 Dec;21(12):3087-99. doi: 10.1210/me.2006-0476. Epub 2007 Aug 30.
5
Identification of amino acid residues within the C terminus of the Glut4 glucose transporter that are essential for insulin-stimulated redistribution to the plasma membrane.鉴定Glut4葡萄糖转运蛋白C末端内的氨基酸残基，这些残基对于胰岛素刺激的向质膜的重新分布至关重要。
J Biol Chem. 2008 May 2;283(18):12571-85. doi: 10.1074/jbc.M800838200. Epub 2008 Feb 27.
6
Dual Function of PI(4,5)P in Insulin-Regulated Exocytic Trafficking of GLUT4 in Adipocytes.PI(4,5)P2 在脂肪细胞胰岛素调节的 GLUT4 胞吐作用中的双重功能。
J Mol Biol. 2020 Jul 24;432(16):4341-4357. doi: 10.1016/j.jmb.2020.06.019. Epub 2020 Jun 25.
7
Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism.铬通过一种胆固醇依赖机制激活葡萄糖转运蛋白4的转运，并增强3T3-L1脂肪细胞中胰岛素刺激的葡萄糖转运。
Mol Endocrinol. 2006 Apr;20(4):857-70. doi: 10.1210/me.2005-0255. Epub 2005 Dec 8.
8
Insulin and chromium picolinate induce translocation of CD36 to the plasma membrane through different signaling pathways in 3T3-L1 adipocytes, and with a differential functionality of the CD36.胰岛素和吡啶甲酸铬通过不同的信号通路诱导 3T3-L1 脂肪细胞中 CD36 向质膜转位，并且 CD36 的功能也不同。
Biol Trace Elem Res. 2011 Sep;142(3):735-47. doi: 10.1007/s12011-010-8809-8. Epub 2010 Aug 19.
9
Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes.肌球蛋白 IIA 参与了 3T3-L1 脂肪细胞中 Glut4 储存小泡与质膜的对接。
Biochem Biophys Res Commun. 2010 Jan 1;391(1):995-9. doi: 10.1016/j.bbrc.2009.12.004. Epub 2009 Dec 5.
10
Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles.PIKfyve的蛋白激酶B磷酸化作用调控葡萄糖转运蛋白4（GLUT4）囊泡的运输。
J Cell Sci. 2004 Dec 1;117(Pt 25):5985-93. doi: 10.1242/jcs.01517. Epub 2004 Nov 16.
引用本文的文献
1
Palmitoylation: an emerging therapeutic target bridging physiology and disease.棕榈酰化：连接生理与疾病的新兴治疗靶点。
Cell Mol Biol Lett. 2025 Aug 15;30(1):98. doi: 10.1186/s11658-025-00776-w.
2
Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18.棕榈酰化调节剂通过抑制铜死亡驱动透明细胞肾细胞癌的进展：对ZDHHC18作用的见解
Cancer Cell Int. 2025 Jun 23;25(1):230. doi: 10.1186/s12935-025-03882-z.
3
The landscape of renal protein S-acylation in mice with lipid-induced nephrotoxicity.脂质诱导肾毒性小鼠中肾脏蛋白质S-酰化修饰情况
Sci Rep. 2025 Mar 5;15(1):7689. doi: 10.1038/s41598-025-92530-7.
4
Palmitoylation and regulation of potassium-dependent sodium/calcium exchangers (NCKX).棕榈酰化作用与钾依赖性钠/钙交换体（NCKX）的调节
Biosci Rep. 2025 Jan 30;45(1):1-11. doi: 10.1042/BSR20241051.
5
Mechanisms and functions of protein S-acylation.蛋白质 S-酰化的机制和功能。
Nat Rev Mol Cell Biol. 2024 Jun;25(6):488-509. doi: 10.1038/s41580-024-00700-8. Epub 2024 Feb 14.
6
Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.色氨酸酰化胰岛素受体由 WARS 减弱胰岛素信号。
Cell Mol Life Sci. 2024 Jan 12;81(1):25. doi: 10.1007/s00018-023-05082-2.
7
Metabolic transitions regulate global protein fatty acylation.代谢转换调节全球蛋白质脂肪酸酰化。
J Biol Chem. 2024 Jan;300(1):105563. doi: 10.1016/j.jbc.2023.105563. Epub 2023 Dec 13.
8
Inter-organ crosstalk during development and progression of type 2 diabetes mellitus.2型糖尿病发生发展过程中的器官间串扰。
Nat Rev Endocrinol. 2024 Jan;20(1):27-49. doi: 10.1038/s41574-023-00898-1. Epub 2023 Oct 16.
9
Palmitoylation of solute carriers.溶质载体的棕榈酰化。
Biochem Pharmacol. 2023 Sep;215:115695. doi: 10.1016/j.bcp.2023.115695. Epub 2023 Jul 20.
10
Visualization of multiple localizations of GLUT4 by fluorescent probes of PYP-tag with designed unnatural warhead.利用带有设计的非天然弹头的PYP标签荧光探针可视化GLUT4的多个定位。
Chem Sci. 2023 May 15;14(22):5925-5935. doi: 10.1039/d3sc00724c. eCollection 2023 Jun 7.
本文引用的文献
1
A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis.棕色脂肪组织生物学的新纪元：棕色脂肪发育和能量平衡的分子调控。
Annu Rev Physiol. 2014;76:225-49. doi: 10.1146/annurev-physiol-021113-170252. Epub 2013 Nov 4.
2
DHHC17 palmitoylates ClipR-59 and modulates ClipR-59 association with the plasma membrane.DHHC17 棕榈酰化 ClipR-59，并调节 ClipR-59 与质膜的结合。
Mol Cell Biol. 2013 Nov;33(21):4255-65. doi: 10.1128/MCB.00527-13. Epub 2013 Sep 3.
3
The LIM domain only 4 protein is a metabolic responsive inhibitor of protein tyrosine phosphatase 1B that controls hypothalamic leptin signaling.LIM 结构域只有 4 蛋白是一种代谢反应性的蛋白酪氨酸磷酸酶 1B 抑制剂，它控制着下丘脑瘦素信号。
J Neurosci. 2013 Jul 31;33(31):12647-55. doi: 10.1523/JNEUROSCI.0746-13.2013.
4
Proteomic analysis of protein palmitoylation in adipocytes.脂肪细胞中蛋白质棕榈酰化的蛋白质组学分析。
Adipocyte. 2013;2(1):17-28. doi: 10.4161/adip.22117.
5
The role of palmitoylation in regulating Ras localization and function.棕榈酰化在调节 Ras 定位和功能中的作用。
Biochem Soc Trans. 2013 Feb 1;41(1):79-83. doi: 10.1042/BST20120268.
6
Glucose transporters in cancer metabolism.癌症代谢中的葡萄糖转运蛋白。
Curr Opin Oncol. 2012 Nov;24(6):650-4. doi: 10.1097/CCO.0b013e328356da72.
7
The association of ClipR-59 protein with AS160 modulates AS160 protein phosphorylation and adipocyte Glut4 protein membrane translocation.ClipR-59 蛋白与 AS160 的关联调节 AS160 蛋白磷酸化和脂肪细胞 Glut4 蛋白的膜转位。
J Biol Chem. 2012 Aug 3;287(32):26890-900. doi: 10.1074/jbc.M112.357699. Epub 2012 Jun 11.
8
Regulation of glucose transport by insulin: traffic control of GLUT4.胰岛素对葡萄糖转运的调节：GLUT4 的交通控制。
Nat Rev Mol Cell Biol. 2012 May 23;13(6):383-96. doi: 10.1038/nrm3351.
9
A role for aberrant protein palmitoylation in FFA-induced ER stress and β-cell death.异常蛋白棕榈酰化在游离脂肪酸诱导的内质网应激和β细胞死亡中的作用。
Am J Physiol Endocrinol Metab. 2012 Jun 1;302(11):E1390-8. doi: 10.1152/ajpendo.00519.2011. Epub 2012 Mar 20.
10
DHHC protein S-acyltransferases use similar ping-pong kinetic mechanisms but display different acyl-CoA specificities.DHHC 蛋白 S-酰基转移酶使用相似的乒乓反应动力学机制，但显示出不同的酰基辅酶 A 特异性。
J Biol Chem. 2012 Mar 2;287(10):7236-45. doi: 10.1074/jbc.M111.337246. Epub 2012 Jan 13.
Zotero 插件