Roles of DGKs in Neurons: Postsynaptic Functions?

Overview

Journal Adv Biol Regul

Publisher Elsevier

Specialties Biochemistry
Molecular Biology

Date 2019 Dec 15

PMID 31836314

Citations 4

Authors

Casey N Barber

Daniel M Raben

Affiliations

Soon will be listed here.

Abstract

Diacylglycerol kinases (DGKs) contribute to an important part of intracellular signaling because, in addition to reducing diacylglycerol levels, they generate phosphatidic acid (PtdOH) Recent research has led to the discovery of ten mammalian DGK isoforms, all of which are found in the mammalian brain. Many of these isoforms have studied functions within the brain, while others lack such understanding in regards to neuronal roles, regulation, and structural dynamics. However, while previously a neuronal function for DGKθ was unknown, it was recently found that DGKθ is required for the regulation of synaptic vesicle endocytosis and work is currently being conducted to elucidate the mechanism behind this regulation. Here we will review some of the roles of all mammalian DGKs and hypothesize additional roles. We will address the topic of redundancy among the ten DGK isoforms and discuss the possibility that DGKθ, among other DGKs, may have unstudied postsynaptic functions. We also hypothesize that in addition to DGKθ's presynaptic endocytic role, DGKθ might also regulate the endocytosis of AMPA receptors and other postsynaptic membrane proteins.

Citing Articles

Identification of Synaptic DGKθ Interactors That Stimulate DGKθ Activity.

Barber C, Goldschmidt H, Ma Q, DeVine L, Cole R, Huganir R Front Synaptic Neurosci. 2022; 14:855673.

PMID: 35573662 PMC: 9095502. DOI: 10.3389/fnsyn.2022.855673.

Advances in chemical proteomic evaluation of lipid kinases-DAG kinases as a case study.

Ware T, Hsu K Curr Opin Chem Biol. 2021; 65:101-108.

PMID: 34311404 PMC: 8671151. DOI: 10.1016/j.cbpa.2021.06.007.

Precise Regulation of the Basal PKCγ Activity by DGKγ Is Crucial for Motor Coordination.

Tsumagari R, Maruo K, Kakizawa S, Ueda S, Yamanoue M, Saito H Int J Mol Sci. 2020; 21(21).

PMID: 33114041 PMC: 7660329. DOI: 10.3390/ijms21217866.

Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling.

Sim J, Kim J, Yang D Int J Mol Sci. 2020; 21(18).

PMID: 32962151 PMC: 7554708. DOI: 10.3390/ijms21186861.

References

Topham M, Prescott S . Mammalian diacylglycerol kinases, a family of lipid kinases with signaling functions. J Biol Chem. 1999; 274(17):11447-50. DOI: 10.1074/jbc.274.17.11447. View

Baum A, Akula N, Cabanero M, Cardona I, Corona W, Klemens B . A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry. 2007; 13(2):197-207. PMC: 2527618. DOI: 10.1038/sj.mp.4002012. View

Ding L, Bunting M, Topham M, McIntyre T, Zimmerman G, Prescott S . Alternative splicing of the human diacylglycerol kinase zeta gene in muscle. Proc Natl Acad Sci U S A. 1997; 94(11):5519-24. PMC: 20810. DOI: 10.1073/pnas.94.11.5519. View

Shulga Y, Topham M, Epand R . Substrate specificity of diacylglycerol kinase-epsilon and the phosphatidylinositol cycle. FEBS Lett. 2011; 585(24):4025-8. PMC: 3237191. DOI: 10.1016/j.febslet.2011.11.016. View

Kai M, Yamamoto E, Sato A, Yamano H, Niinuma T, Kitajima H . Epigenetic silencing of diacylglycerol kinase gamma in colorectal cancer. Mol Carcinog. 2017; 56(7):1743-1752. DOI: 10.1002/mc.22631. View

Zeng Z, Wang T, Li T, Li Y, Chen P, Zhao Q . Common SNPs and haplotypes in DGKH are associated with bipolar disorder and schizophrenia in the Chinese Han population. Mol Psychiatry. 2010; 16(5):473-5. DOI: 10.1038/mp.2010.86. View

Purow B . Molecular Pathways: Targeting Diacylglycerol Kinase Alpha in Cancer. Clin Cancer Res. 2015; 21(22):5008-12. PMC: 4644682. DOI: 10.1158/1078-0432.CCR-15-0413. View

Takeishi K, Taketomi A, Shirabe K, Toshima T, Motomura T, Ikegami T . Diacylglycerol kinase alpha enhances hepatocellular carcinoma progression by activation of Ras-Raf-MEK-ERK pathway. J Hepatol. 2012; 57(1):77-83. DOI: 10.1016/j.jhep.2012.02.026. View

Kim K, Yang J, Zhong X, Kim M, Kim Y, Lee H . Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance. EMBO J. 2009; 28(8):1170-9. PMC: 2683696. DOI: 10.1038/emboj.2009.44. View

10.

Lowe C, Zhang Q, Dennis R, Aubry E, ORahilly S, Wakelam M . Knockdown of diacylglycerol kinase delta inhibits adipocyte differentiation and alters lipid synthesis. Obesity (Silver Spring). 2013; 21(9):1823-9. PMC: 3763967. DOI: 10.1002/oby.20297. View

11.

Caricasole A, Bettini E, Sala C, Roncarati R, Kobayashi N, Caldara F . Molecular cloning and characterization of the human diacylglycerol kinase beta (DGKbeta) gene: alternative splicing generates DGKbeta isotypes with different properties. J Biol Chem. 2001; 277(7):4790-6. DOI: 10.1074/jbc.M110249200. View

12.

Kai M, Sakane F, Imai S, Wada I, Kanoh H . Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in human retina with a truncated and inactive enzyme expression in most other human cells. J Biol Chem. 1994; 269(28):18492-8. View

13.

Ollila H, Soronen P, Silander K, Palo O, Kieseppa T, Kaunisto M . Findings from bipolar disorder genome-wide association studies replicate in a Finnish bipolar family-cohort. Mol Psychiatry. 2009; 14(4):351-3. PMC: 2694406. DOI: 10.1038/mp.2008.122. View

14.

Shirai Y, Saito N . Diacylglycerol kinase as a possible therapeutic target for neuronal diseases. J Biomed Sci. 2014; 21:28. PMC: 4005014. DOI: 10.1186/1423-0127-21-28. View

15.

Malenka R, Bear M . LTP and LTD: an embarrassment of riches. Neuron. 2004; 44(1):5-21. DOI: 10.1016/j.neuron.2004.09.012. View

16.

Squassina A, Manchia M, Congiu D, Severino G, Chillotti C, Ardau R . The diacylglycerol kinase eta gene and bipolar disorder: a replication study in a Sardinian sample. Mol Psychiatry. 2009; 14(4):350-1. DOI: 10.1038/mp.2008.93. View

17.

Rosendale M, Jullie D, Choquet D, Perrais D . Spatial and Temporal Regulation of Receptor Endocytosis in Neuronal Dendrites Revealed by Imaging of Single Vesicle Formation. Cell Rep. 2017; 18(8):1840-1847. DOI: 10.1016/j.celrep.2017.01.081. View

18.

Zhang N, Li B, Al-Ramahi I, Cong X, Held J, Kim E . Inhibition of lipid signaling enzyme diacylglycerol kinase epsilon attenuates mutant huntingtin toxicity. J Biol Chem. 2012; 287(25):21204-13. PMC: 3375542. DOI: 10.1074/jbc.M111.321661. View

19.

Crotty T, Cai J, Sakane F, Taketomi A, Prescott S, Topham M . Diacylglycerol kinase delta regulates protein kinase C and epidermal growth factor receptor signaling. Proc Natl Acad Sci U S A. 2006; 103(42):15485-90. PMC: 1622849. DOI: 10.1073/pnas.0604104103. View

20.

Leach N, Sun Y, Michaud S, Zheng Y, Ligon K, Ligon A . Disruption of diacylglycerol kinase delta (DGKD) associated with seizures in humans and mice. Am J Hum Genet. 2007; 80(4):792-9. PMC: 1852716. DOI: 10.1086/513019. View