Diacylglycerol (DAG) Signaling Role in Synaptic Plasticity
Introduction of DAG
Diacylglycerol (DAG) is made up of a glycerol backbone esterified with two fatty acids, giving rise to the formation of three stereochemical isoforms namely sn-1,2-DAG, sn1,3-DAG, and sn-2,3-DAG. Among the three isomers, 1,3-DAG is thermodynamically more stable as compared to 1,2-(2,3-)-DAG due to the steric hindrance effect. Hence, it is common to end up with an equilibrium mixture of 30-40% 1,2-(2,3-) DAG and 60-70% 1,3-DAG. sn-1,2-Diacylglycerol is the most studied diradylglycerol in mammalian cells. The lipid plays a key role in lipid biosynthesis, in particular of phospholipids and triglycerides, but its individual significance is a consequence of its identification as the physiological activator of protein kinase C (PKC). There are three diradylglycerols in mammalian cells, alkyl, acyl-glycerol, alkenyl, acyl-glycerol, and DAG.
Fig.1 DAG digestion pathway.1
Introduction of Synaptic Plasticity
This plasticity determines the ability to alter responsiveness under the influence of successive stimuli, either directly or in association with other factors. Plasticity is the fundamental and most specific functional characteristic of nerve cells, switching on diverse changes in the functioning of neurons. The plastic alterations result in prolonged cellular and synaptic function modifications, which allow us to explain simple modifications of behavioral reactions. The plasticity of the neuron can manifest in the form of a temporary alteration in its responsiveness, either depression or an enhancement. These forms of plasticity, in turn, can be classified into synaptic forms presupposing previous synaptic activation and nonsynaptic forms, which occur when plasticity arises after direct (chemical or electrical) stimulation of the neuron.
DAG Signaling Role in Synaptic Plasticity
It has been long recognized that lipids play important roles in a number of physiological functions. The discovery of the phosphatidylinositol (PtdIns) cycle in neurons accelerated research on the role of lipids in neurobiology. The canonical view of the PtdIns cycle involves the stimulated hydrolysis of phosphatidylinositol-(4,5) bisphosphate PtdIns(4,5)P2 which leads to the generation of inositol (1,4,5) trisphosphate (IP3) and DAG. This system, along with an influx of extracellular calcium provides a mechanism for stimulated increases in calcium and DAG during neuronal stimulation. The DAG generated in this cycle is converted to phosphatidic acid (PtdOH) which is subsequently used for the re-synthesis of PtdIns. Enzymes capable of coordinately regulating the levels of these two lipids are the diacylglycerol kinases (DGKs). These enzymes are organized into five classes or Types based upon similarities in their primary sequence. All DGKs catalyze the transfer of the γ-phosphate of ATP to the hydroxyl group of DAG thereby generating PtdOH while reducing DAG. The notion that these enzymes play important neuronal roles is supported by the observations that eight of the 10 mammalian DGK isozymes are readily detected in the mammalian central nervous system (CNS).
Fig.2 Possible distinct functions of DGK isoforms and their general role in coordinating synaptic plasticity.1
Table 1. Involvement of DGK isoforms in several forms of synaptic plasticity.
DGK isoform |
Synapse | Localization | Tested forms of synaptic plasticity | Reported effects in KO mice | Known/expected functions of DGKs |
DGKε | Perforant path-dentate granule cell synapses | N.D. | LTP | Reduction | Regulating amounts of DAG and PKC activity required for LTP, and regulating the lipid signaling leading to the production of retrograde messengers required for LTP |
DGKζ | Hippocampal SC-CA1 synapses | Postsynaptic density | Postsynaptic LTP | Enhancement | Regulating amounts of DAG produced by mGluR activation, and balancing PKC activity, which is a modulator of LTP and LTD |
Postsynaptic LTD | Reduction | – | |||
DGKβ | Hippocampal SC-CA1 synapses | Membranes including synaptic areas | Postsynaptic LTP | Reduction | Regulating basal DAG levels |
DGKι | Hippocampal SC-CA1 synapses | Presynaptic areas | Presynaptic LTD | Reduction | Reducing DAG levels and consequently preventing the activation of target molecules that antagonize LTD |
DGKκ | Hippocampal SC-CA1 synapses | N.D. | Postsynaptic LTP | Reduction | Regulating basal DAG levels |
Postsynaptic LTD | Enhancement | – | |||
DGKζ |
Cerebellar parallel fiber-Purkinje cell synapses |
Postsynaptic areas | Postsynaptic LTP | Normal | – |
Postsynaptic LTD | Reduction | Targeting PKCα required for LTD at synapses, maintaining optimal PKCα activity levels via reducing basal DAG levels, and receiving inhibition from PKCα |
Creative Biolabs is an experienced neuro-based service and products provider. We have rich experience in neuro research and have established a neuro-based platform providing relevant products as well as services. Every effort we made is to provide our customers with a comprehensive and comfortable one-stop service.
If you are interested in neuro researches and relevant services, or you have any other questions, please don’t hesitate to contact us for more information.
Reference
- Lee, Dongwon, Eunjoon Kim, and Keiko Tanaka-Yamamoto. "Diacylglycerol kinases in the coordination of synaptic plasticity." Frontiers in cell and developmental biology 4 (2016): 92. Distributed under Open Access license CC BY 4.0, without modification.
- iNeuMab™ Rabbit Anti-Alpha-synuclein (CBP1631) (Cat#: NAB-08-PZ079)
- iNeuMab™ Anti-SEZ6 Antibody (NRP-0422-P517) (Cat#: NRP-0422-P517)
- iNeuMab™ Rabbit Anti-LRRK2 Monoclonal Antibody (CBP1887) (Cat#: NAB-08-PZ735)
- iNeuMab™ Anti-Tau Antibody (NRP-0422-P1686) (Cat#: NRP-0422-P1686)
- iNeuMab™ Anti-F-Spondin/SPON1 Antibody, Clone 3F4 (Cat#: NRZP-0822-ZP4740)
- iNeuMab™ Anti-TREM2 BBB Shuttle Antibody (NRZP-1022-ZP4114) (Cat#: NRZP-1022-ZP4114)
- iNeuMab™ Anti-ApoC3 BBB Shuttle Antibody (NRZP-1022-ZP3505) (Cat#: NRZP-1022-ZP3505)
- iNeuMab™ Anti-CD20 Antibody (NRP-0422-P1230) (Cat#: NRP-0422-P1230)
- iNeuMab™ Anti-CD32b Antibody (NRP-0422-P1803) (Cat#: NRP-0422-P1803)
- iNeuMab™ Anti-EPHB2 Antibody (NRP-0422-P1220) (Cat#: NRP-0422-P1220)
- Human Blood Brain Barrier Model (Cat#: NCL-2103-P187)
- Mouse Microglia N9 (Cat#: NCL2110P073)
- iNeu™ Human Oligodendrocyte Progenitor Cells (OPCs) (Cat#: NCL-2103-P49)
- Human Retinal Epithelial Cell ARPE-19 (Cat#: NCL2110P069)
- iNeu™ Human Motor Neurons (Cat#: NCL-2103-P71)
- iNeu™ Human Sensory Neurons (Cat#: NCL-2103-P62)
- Mouse Microglia from C57BL/6 (Cat#: NCL-21P6-082)
- Rat Schwann Cells RSC96, Immortalized (Cat#: NCL-2108P21)
- Human Astrocytes (Cat#: NCC20-9PZ01)
- Mouse Microglia Cell Line BV-2, Immortalized (Cat#: NCL2110P153)
- Human Tau Aggregation Kit (Cat#: NRP-0322-P2173)
- Beta Amyloid (1-40), Aggregation Kit (Cat#: NRZP-0323-ZP199)
- Alpha Synuclein Aggregation Kit (Cat#: NRZP-1122-ZP15)
- Amyloid beta 1-42 Kit (Cat#: NRP-0322-P2170)
- Beta Amyloid (1-42), Aggregation Kit (Cat#: NRZP-0323-ZP200)
- Alpha-Synuclein Aggregation Assay Kit (Cat#: NRZP-1122-ZP37)
- Human GFAP ELISA Kit [Colorimetric] (Cat#: NPP2011ZP383)
- Human Poly ADP ribose polymerase,PARP Assay Kit (Cat#: NRZP-1122-ZP62)
- VSV-eGFP (Cat#: NTA-2011-ZP20)
- Dextran, NHS Activated (Cat#: NRZP-0722-ZP124)
- AAV2 Full Capsids, Reference Standards (Cat#: NTC2101070CR)
- App Rat amyloid beta (A4) precursor protein (App)(NM_019288) ORF clone, Untagged (Cat#: NEP-0421-R0053)
- Human apolipoprotein E (APOE) (NM_000041) ORF clone, Untagged (Cat#: NEP-0421-R0232)
- Human huntingtin-associated protein 1 (HAP1) transcript variant 2 (NM_177977) ORF clone, Myc-DDK Tagged (Cat#: NEP-0521-R0676)
- Mouse Parkinson disease (autosomal recessive, early onset) 7 (Park7) (NM_020569) clone, Untagged (Cat#: NEP-0621-R0133)
- Rat Parkinson disease (autosomal recessive, juvenile) 2, parkin (Park2) (NM_020093) ORF clone/lentiviral particle, Myc-DDK Tagged (Cat#: NEP-0621-R0041)
- Human superoxide dismutase 3, extracellular (SOD3) (NM_003102) ORF clone, Untagged (Cat#: NEP-0521-R0808)
- Human superoxide dismutase 1, soluble (SOD1) (NM_000454) ORF clone, TurboGFP Tagged (Cat#: NEP-0521-R0748)
- Human presenilin 1 (PSEN1), transcript variant 2 (NM_007318) ORF clone, TurboGFP Tagged (Cat#: NEP-0421-R0140)
- Lenti of Human TAR DNA binding protein (TARDBP) (NM_007375) ORF clone, mGFP Tagged (Cat#: NEP-0521-R0832)
- ABCA1 Antisense Oligonucleotide (NV-2106-P27) (Cat#: NV-2106-P27)
- NeuroBiologics™ Monkey Cerebrospinal Fluid (Cat#: NRZP-0822-ZP495)
- NeuroBiologics™ Rat Cerebrospinal Fluid (Cat#: NRZP-0822-ZP496)
- NeuroBiologics™ Human Cerebrospinal Fluid (Cat#: NRZP-0822-ZP491)
- NeuroBiologics™ Mouse Cerebrospinal Fluid (Cat#: NRZP-0822-ZP497)
- NeuroBiologics™ Pig Cerebrospinal Fluid (Cat#: NRZP-0822-ZP498)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP500)
- NeuroPro™ Anti-IDUA BBB Shuttle Protein (Cat#: NRZP-0423-ZP502)
- NeuroPro™ Anti-NAGLU BBB Shuttle Protein (Cat#: NRZP-0423-ZP506)
- NeuroPro™ Anti-idursulfase BBB Shuttle Protein (Cat#: NRZP-0423-ZP497)
- NeuroPro™ Anti-EPO BBB Shuttle Protein (Cat#: NRZP-0423-ZP508)
- NeuroPro™ Anti-ASA BBB Shuttle Protein (Cat#: NRZP-0423-ZP504)
- NeuroPro™ Anti-SGSH BBB Shuttle Protein (Cat#: NRZP-0423-ZP505)
- NeuroPro™ Anti-PON1 BBB Shuttle Protein (Cat#: NRZP-0423-ZP507)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP509)
- NeuroPro™ Anti-TNFR BBB Shuttle Protein (Cat#: NRZP-0423-ZP510)