PI3P 磷酸酶在自噬调控中的作用。
The role of PI3P phosphatases in the regulation of autophagy.
机构信息
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
出版信息
FEBS Lett. 2010 Apr 2;584(7):1313-8. doi: 10.1016/j.febslet.2010.02.054. Epub 2010 Feb 24.
Abstract
Autophagy initiation is strictly dependent on phosphatidylinositol 3-phosphate (PI3P) synthesis. PI3P production is under tight control of PI3Kinase, hVps34, in complex with Beclin-1. Mammalian cells express several PI3P phosphatases that belong to the myotubularin family. Even though some of them have been linked to serious human diseases, their cellular function is largely unknown. Two recent studies indicate that PI3P metabolism involved in autophagy initiation is further regulated by the PI3P phosphatases Jumpy and MTMR3. Additional pools of PI3P, upstream of mTOR and on the endocytic pathway, may modulate autophagy indirectly, suggesting that other PI3P phosphatases might be involved in this process. This review sums up our knowledge on PI3P phosphatases and discusses the recent progress on their role in autophagy.
摘要
自噬的起始严格依赖于磷脂酰肌醇 3-磷酸（PI3P）的合成。PI3P 的产生受到 PI3 激酶、与 Beclin-1 形成复合物的 hVps34 的严格控制。哺乳动物细胞表达几种属于肌管素家族的 PI3P 磷酸酶。尽管其中一些已与严重的人类疾病相关联，但它们的细胞功能在很大程度上仍是未知的。最近的两项研究表明，参与自噬起始的 PI3P 代谢进一步受到 PI3P 磷酸酶 Jumpy 和 MTMR3 的调节。mTOR 上游和内吞途径上的其他 PI3P 池可能间接调节自噬，这表明其他 PI3P 磷酸酶可能参与这一过程。本文综述了我们对 PI3P 磷酸酶的了解，并讨论了它们在自噬中的作用的最新进展。
相似文献
1
The role of PI3P phosphatases in the regulation of autophagy.PI3P 磷酸酶在自噬调控中的作用。
FEBS Lett. 2010 Apr 2;584(7):1313-8. doi: 10.1016/j.febslet.2010.02.054. Epub 2010 Feb 24.
2
Regulation of mammalian autophagy by class II and III PI 3-kinases through PI3P synthesis.通过 PI3P 合成调控哺乳动物自噬的 II 类和 III 类 PI3 激酶。
PLoS One. 2013 Oct 3;8(10):e76405. doi: 10.1371/journal.pone.0076405. eCollection 2013.
3
Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics.磷脂酰肌醇-3-磷酸在自噬膜动力学调节中的作用。
FEBS J. 2017 May;284(9):1267-1278. doi: 10.1111/febs.13987. Epub 2017 Jan 5.
4
PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation.PI3P磷酸酶活性是自噬体成熟和自溶酶体形成所必需的。
EMBO Rep. 2014 Sep;15(9):973-81. doi: 10.15252/embr.201438618. Epub 2014 Aug 14.
5
Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway.肌管素是一种在肌管性肌病中缺乏的磷酸酶，作用于磷脂酰肌醇3激酶和磷脂酰肌醇3磷酸途径。
Hum Mol Genet. 2000 Sep 22;9(15):2223-9. doi: 10.1093/oxfordjournals.hmg.a018913.
6
Regulation of membrane biogenesis in autophagy via PI3P dynamics.通过 PI3P 动力学调节自噬中的膜生物发生。
Semin Cell Dev Biol. 2010 Sep;21(7):671-6. doi: 10.1016/j.semcdb.2010.04.002. Epub 2010 Apr 18.
7
Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy.由磷酸肌醇 3-磷酸酶 Jumpy 控制自噬起始。
EMBO J. 2009 Aug 5;28(15):2244-58. doi: 10.1038/emboj.2009.159. Epub 2009 Jul 9.
8
Plasmodium falciparum Atg18 localizes to the food vacuole via interaction with the multi-drug resistance protein 1 and phosphatidylinositol 3-phosphate.恶性疟原虫 Atg18 通过与多药耐药蛋白 1 和磷脂酰肌醇 3-磷酸相互作用定位于食物泡。
Biochem J. 2021 May 14;478(9):1705-1732. doi: 10.1042/BCJ20210001.
9
Elevating PI3P drives select downstream membrane trafficking pathways.PI3P 的升高会驱动下游特定的膜运输途径。
Mol Biol Cell. 2021 Jan 15;32(2):143-156. doi: 10.1091/mbc.E20-03-0191. Epub 2020 Nov 25.
10
Myotubularin 2 interacts with SEC23A and negatively regulates autophagy at ER exit sites in Arabidopsis.肌管素2与SEC23A相互作用，并在拟南芥的内质网出口位点负向调节自噬。
Autophagy. 2025 Jan;21(1):141-159. doi: 10.1080/15548627.2024.2394302. Epub 2024 Sep 8.
引用本文的文献
1
Pharmacological mechanism of natural products to treat osteoporosis: a focus on the autophagy.天然产物治疗骨质疏松症的药理机制：聚焦自噬
Front Pharmacol. 2025 Aug 1;16:1623990. doi: 10.3389/fphar.2025.1623990. eCollection 2025.
2
Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy.线粒体损伤引发神经元自噬负调控因子的协同降解。
Nat Commun. 2025 Aug 9;16(1):7367. doi: 10.1038/s41467-025-62379-5.
3
Association of MTMR3 rs12537 at miR-181a Binding Site with Ischemic Stroke in Southern Chinese Han Population.位于miR-181a结合位点的MTMR3基因rs12537与中国南方汉族人群缺血性脑卒中的关联
Int J Gen Med. 2025 May 22;18:2659-2672. doi: 10.2147/IJGM.S524033. eCollection 2025.
4
Whole genome sequencing analysis of body mass index identifies novel African ancestry-specific risk allele.体重指数的全基因组测序分析确定了新的非洲血统特异性风险等位基因。
Nat Commun. 2025 Apr 11;16(1):3470. doi: 10.1038/s41467-025-58420-2.
5
Unraveling the role of autophagy regulation in Crohn's disease: from genetic mechanisms to potential therapeutics.解析自噬调节在克罗恩病中的作用：从遗传机制到潜在治疗方法
Adv Biotechnol (Singap). 2024 Mar 21;2(2):14. doi: 10.1007/s44307-024-00021-z.
6
Lipids associated with autophagy: mechanisms and therapeutic targets.与自噬相关的脂质：机制与治疗靶点。
Cell Death Discov. 2024 Oct 30;10(1):460. doi: 10.1038/s41420-024-02224-8.
7
Stimulative piezoelectric nanofibrous scaffolds for enhanced small extracellular vesicle production in 3D cultures.刺激响应性压电纳米纤维支架促进 3D 培养中小细胞外囊泡的高效生产。
Biomater Sci. 2024 Nov 5;12(22):5728-5741. doi: 10.1039/d4bm00504j.
8
The roles and mechanisms of endoplasmic reticulum stress-mediated autophagy in animal viral infections.内质网应激介导的自噬在动物病毒感染中的作用及其机制。
Vet Res. 2024 Sep 3;55(1):107. doi: 10.1186/s13567-024-01360-4.
9
Roles of lipid droplets and related proteins in metabolic diseases.脂滴及其相关蛋白在代谢性疾病中的作用。
Lipids Health Dis. 2024 Jul 19;23(1):218. doi: 10.1186/s12944-024-02212-y.
10
Uropathogenic Escherichia coli Subverts Host Autophagic Defenses by Stalling Preautophagosomal Structures to Escape Lysosome Exocytosis.尿路致病性大肠杆菌通过使前自噬体结构停滞来逃避溶酶体胞吐作用，从而颠覆宿主的自噬防御。
J Infect Dis. 2024 Sep 23;230(3):e548-e558. doi: 10.1093/infdis/jiae063.
本文引用的文献
1
FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end-directed vesicle transport.FYCO1 是一种 Rab7 效应物，它与 LC3 和 PI3P 结合，介导微管正极定向囊泡运输。
J Cell Biol. 2010 Jan 25;188(2):253-69. doi: 10.1083/jcb.200907015.
2
Modulation of local PtdIns3P levels by the PI phosphatase MTMR3 regulates constitutive autophagy.通过 PI 磷酸酶 MTMR3 调节局部 PtdIns3P 水平来调节组成型自噬。
Traffic. 2010 Apr;11(4):468-78. doi: 10.1111/j.1600-0854.2010.01034.x. Epub 2010 Jan 6.
3
The CMT4B disease-causing proteins MTMR2 and MTMR13/SBF2 regulate AKT signalling.CMT4B 病致病蛋白 MTMR2 和 MTMR13/SBF2 调节 AKT 信号通路。
J Cell Mol Med. 2011 Feb;15(2):307-15. doi: 10.1111/j.1582-4934.2009.00967.x.
4
T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase.缺乏肌管素脂质磷酸酶的肌纤维中T小管紊乱及兴奋-收缩偶联缺陷。
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18763-8. doi: 10.1073/pnas.0900705106. Epub 2009 Oct 21.
5
Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes.多种III类磷脂酰肌醇3-激酶复合物在自噬过程中对膜事件的协调作用。
J Cell Biol. 2009 Sep 21;186(6):773-82. doi: 10.1083/jcb.200907014.
6
Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2.PI(3,5)P2 缺乏的神经元和星形胶质细胞中的自噬缺陷。
Hum Mol Genet. 2009 Dec 15;18(24):4868-78. doi: 10.1093/hmg/ddp460. Epub 2009 Sep 29.
7
Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy.由磷酸肌醇 3-磷酸酶 Jumpy 控制自噬起始。
EMBO J. 2009 Aug 5;28(15):2244-58. doi: 10.1038/emboj.2009.159. Epub 2009 Jul 9.
8
Dlg1, Sec8, and Mtmr2 regulate membrane homeostasis in Schwann cell myelination.Dlg1、Sec8和Mtmr2在施万细胞髓鞘形成过程中调节膜稳态。
J Neurosci. 2009 Jul 8;29(27):8858-70. doi: 10.1523/JNEUROSCI.1423-09.2009.
9
PIKfyve regulation of endosome-linked pathways.内体连接途径的PIKfyve调控
Traffic. 2009 Jul;10(7):883-93. doi: 10.1111/j.1600-0854.2009.00915.x.
10
The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy.钙离子通道TRPML3调节膜转运和自噬。
Traffic. 2009 Aug;10(8):1157-67. doi: 10.1111/j.1600-0854.2009.00924.x. Epub 2009 May 11.
Zotero 插件