MARK/Par1激酶通过依赖蛋白激酶A的机制在N-甲基-D-天冬氨酸受体下游被激活。
MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism.
作者信息
Bernard Laura P, Zhang Huaye
机构信息
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, New Jersey, United States of America.
出版信息
PLoS One. 2015 May 1;10(5):e0124816. doi: 10.1371/journal.pone.0124816. eCollection 2015.
Abstract
The Par1 kinases, also known as microtubule affinity-regulating kinases (MARKs), are important for the establishment of cell polarity from worms to mammals. Dysregulation of these kinases has been implicated in autism, Alzheimer's disease and cancer. Despite their important function in health and disease, it has been unclear how the activity of MARK/Par1 is regulated by signals from cell surface receptors. Here we show that MARK/Par1 is activated downstream of NMDA receptors in primary hippocampal neurons. Further, we show that this activation is dependent on protein kinase A (PKA), through the phosphorylation of Ser431 of Par4/LKB1, the major upstream kinase of MARK/Par1. Together, our data reveal a novel mechanism by which MARK/Par1 is activated at the neuronal synapse.
摘要
Par1激酶，也被称为微管亲和力调节激酶（MARKs），对于从蠕虫到哺乳动物的细胞极性建立至关重要。这些激酶的失调与自闭症、阿尔茨海默病和癌症有关。尽管它们在健康和疾病中具有重要功能，但尚不清楚MARK/Par1的活性是如何受到细胞表面受体信号调节的。在这里，我们表明MARK/Par1在原代海马神经元中在NMDA受体下游被激活。此外，我们表明这种激活依赖于蛋白激酶A（PKA），通过Par4/LKB1（MARK/Par1的主要上游激酶）的Ser431位点磷酸化实现。总之，我们的数据揭示了一种在神经元突触处激活MARK/Par1的新机制。
相似文献
1
MARK/Par1 Kinase Is Activated Downstream of NMDA Receptors through a PKA-Dependent Mechanism.
PLoS One. 2015 May 1;10(5):e0124816. doi: 10.1371/journal.pone.0124816. eCollection 2015.
2
NMDA receptor activation results in PKA- and ERK-dependent Mnk1 activation and increased eIF4E phosphorylation in hippocampal area CA1.
J Neurochem. 2004 Oct;91(2):462-70. doi: 10.1111/j.1471-4159.2004.02734.x.
3
Ethanol inhibition of NMDA receptors under conditions of altered protein kinase A activity.
J Neurochem. 2006 Mar;96(6):1760-7. doi: 10.1111/j.1471-4159.2006.03703.x.
4
Protein kinase A regulates calcium permeability of NMDA receptors.
Nat Neurosci. 2006 Apr;9(4):501-10. doi: 10.1038/nn1664. Epub 2006 Mar 12.
5
Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.
Gastroenterology. 2012 Apr;142(4):834-843.e3. doi: 10.1053/j.gastro.2011.12.053. Epub 2012 Jan 12.
6
Dexmedetomidine prevents post-ischemic LTP via presynaptic and postsynaptic mechanisms.
Brain Res. 2015 Oct 5;1622:308-20. doi: 10.1016/j.brainres.2015.06.040. Epub 2015 Jul 10.
7
BRSK2 is activated by cyclic AMP-dependent protein kinase A through phosphorylation at Thr260.
Biochem Biophys Res Commun. 2006 Sep 8;347(4):867-71. doi: 10.1016/j.bbrc.2006.06.178. Epub 2006 Jul 25.
8
Neuronal transmission stimulates the phosphorylation of Kv1.4 channel at Ser229 through protein kinase A1.
J Neurochem. 2005 Sep;94(6):1512-22. doi: 10.1111/j.1471-4159.2005.03297.x. Epub 2005 Jul 5.
9
Protease activated receptor 1 (PAR1) enhances Src-mediated tyrosine phosphorylation of NMDA receptor in intracerebral hemorrhage (ICH).
Sci Rep. 2016 Jul 7;6:29246. doi: 10.1038/srep29246.
10
Synergistic interactions of dopamine D1 and glutamate NMDA receptors in rat hippocampus and prefrontal cortex: involvement of ERK1/2 signaling.
Neuroscience. 2009 Nov 10;163(4):1135-45. doi: 10.1016/j.neuroscience.2009.07.056. Epub 2009 Jul 30.
引用本文的文献
1
Liver kinase B-1 modulates the activity of dopamine neurons in the ventral tegmental area and regulates social memory formation.
Front Mol Neurosci. 2024 Apr 5;17:1289476. doi: 10.3389/fnmol.2024.1289476. eCollection 2024.
2
MARK1 regulates dendritic spine morphogenesis and cognitive functions in vivo.
Exp Neurol. 2024 Jun;376:114752. doi: 10.1016/j.expneurol.2024.114752. Epub 2024 Mar 12.
3
Liver Kinase B1 Functions as a Regulator for Neural Development and a Therapeutic Target for Neural Repair.
Cells. 2022 Sep 14;11(18):2861. doi: 10.3390/cells11182861.
4
Polarity proteins: Shaping dendritic spines and memory.
Dev Biol. 2022 Aug;488:68-73. doi: 10.1016/j.ydbio.2022.05.007. Epub 2022 May 14.
5
Metformin reduces neuroinflammation and improves cognitive functions after traumatic brain injury.
Neurosci Res. 2021 Nov;172:99-109. doi: 10.1016/j.neures.2021.05.007. Epub 2021 May 21.
6
Memantine Improves Cognitive Function and Alters Hippocampal and Cortical Proteome in Triple Transgenic Mouse Model of Alzheimer's Disease.
Exp Neurobiol. 2019 Jun;28(3):390-403. doi: 10.5607/en.2019.28.3.390. Epub 2019 Jun 26.
7
Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons.
Neurobiol Aging. 2019 May;77:87-93. doi: 10.1016/j.neurobiolaging.2019.01.023. Epub 2019 Jan 30.
8
Loss of Par1b/MARK2 primes microglia during brain development and enhances their sensitivity to injury.
J Neuroinflammation. 2019 Jan 17;16(1):11. doi: 10.1186/s12974-018-1390-3.
9
Role of Microtubule-Associated Protein in Autism Spectrum Disorder.
Neurosci Bull. 2018 Dec;34(6):1119-1126. doi: 10.1007/s12264-018-0246-2. Epub 2018 Jun 23.
10
Par3 and aPKC regulate BACE1 endosome-to-TGN trafficking through PACS1.
Neurobiol Aging. 2017 Dec;60:129-140. doi: 10.1016/j.neurobiolaging.2017.08.024. Epub 2017 Sep 21.
本文引用的文献
1
p140Cap regulates memory and synaptic plasticity through Src-mediated and citron-N-mediated actin reorganization.
J Neurosci. 2014 Jan 22;34(4):1542-53. doi: 10.1523/JNEUROSCI.2341-13.2014.
2
Dendritic spines: the locus of structural and functional plasticity.
Physiol Rev. 2014 Jan;94(1):141-88. doi: 10.1152/physrev.00012.2013.
3
Calcium phosphate transfection of primary hippocampal neurons.
J Vis Exp. 2013 Nov 12(81):e50808. doi: 10.3791/50808.
4
Plasticity of dendritic spines: subcompartmentalization of signaling.
Annu Rev Physiol. 2014;76:365-85. doi: 10.1146/annurev-physiol-021113-170400. Epub 2013 Nov 6.
5
Synaptic NMDA receptor stimulation activates PP1 by inhibiting its phosphorylation by Cdk5.
J Cell Biol. 2013 Nov 11;203(3):521-35. doi: 10.1083/jcb.201303035. Epub 2013 Nov 4.
6
The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).
J Biol Chem. 2012 Aug 31;287(36):30781-8. doi: 10.1074/jbc.M112.351452. Epub 2012 Jul 17.
7
Opposite effects of fear conditioning and extinction on dendritic spine remodelling.
Nature. 2012 Feb 19;483(7387):87-91. doi: 10.1038/nature10792.
8
Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo.
Nature. 2012 Feb 19;483(7387):92-5. doi: 10.1038/nature10844.
9
Mechanisms of CaMKII action in long-term potentiation.
Nat Rev Neurosci. 2012 Feb 15;13(3):169-82. doi: 10.1038/nrn3192.
10
A critical role for the PAR-1/MARK-tau axis in mediating the toxic effects of Aβ on synapses and dendritic spines.
Hum Mol Genet. 2012 Mar 15;21(6):1384-90. doi: 10.1093/hmg/ddr576. Epub 2011 Dec 8.
Zotero 插件