Calcium-Calmodulin Kinase in Learning and Memory
The neural mechanism of learning and memory has always been a hot topic for scientists. In 1971, Giacobini proposed the theory of synaptic plasticity, which believed that the structure and number of synapses in the brain and the transmission effect between synapses will change during the process of learning and memory. In 1973, Bliss discovered that tetanic stimulation could induce the facilitation of synaptic transmission that lasts more than 10 hours in anesthetized rabbits, which is long-term potentiation (LTP). In the early 1990s, Linch et al. found that animals' memory after behavioral training was always accompanied by the appearance of LTP, which was named learned LTP. Further research showed that LTP is widely present in the brain structure closely related to learning and memory activities. Later, through many experiments, scientists discovered a memory “molecular switch”, calcium/calmodulin-dependent protein kinase II (CaM kinase II or CaMKII). During learning, the enzyme is activated by phosphorylation and catalyzes autophosphorylation, so that the kinase can remain active for a long time after learning.
Introduction of CaMKII
CaMKII is a serine/threonine-specific protein kinase regulated by the Ca2+ /calmodulin complex. It is involved in many signaling cascades and is an important regulator in learning and memory. CaMKII plays an important role in Ca2+ homeostasis and reuptake in cardiomyocytes, transportation of chloride ion in epithelial cells, selection of positive T cell, and activation of CD8 T cell.
Fig.1 CaMKII gamma holoenzyme in its (A) closed and the (B) open conformations.
- Types
Specialized CaM kinases: such as myosin light chain kinase which involves smooth muscle contraction through phosphorylating myosin.
Multifunctional CaM kinases: involves transcription factor regulation, neurotransmitter secretion, and glycogen metabolism.
Isoforms | Function |
CaMK2A | Major forms of CamKII, involves sustaining activation of CamKII at the postsynaptic density |
CaMK2B | As a targeting or docking module, Contain an autophosphorylation site at Thr287 |
CaMK2D | Present in both neuronal and non-neuronal cell types, also found in many tumor cells |
CaMK2G | A crucial extracellular signal-regulated kinase in differentiated smooth muscle cells |
- Structure
Domain | Characterization |
Catalytic Domain | The catalytic domain, containing several binding sites for ATP and other substrate-anchored proteins, functions to transfer a phosphate from ATP to serine or threonine residues in substances. |
Autoinhibitory Domain | Characterized by a pseudosubstrate site that can bind to the catalytic domain and inhibit its binding to phosphorylate proteins. |
Variable Segment | Associated with the various CaMKII isoforms. |
Self-Association Domain | Found at the C terminus and involves the assembly of the single proteins into large multimers |
Function of CaMKII in LTP
In an excitatory synapse, the formation of LTP includes two stages, namely the early induction stage, and the late maintenance stage.
- Induction of LTP
The increase of presynaptic glutamate transmitter release and enhancement of post-synaptic depolarization could activate the glutamate receptor-NMDA complex on the postsynaptic membrane. Ca2+ ions could enter the postsynaptic cell through the NMDA receptor. CaMKII can recognize the increased signals of Ca2+ ions and autophosphorylation occurs when the Ca2+ is continuously increased to a certain concentration, thereby forming a stable open state, and inducing a series of biochemical reactions related to Ca2+, finally inducing LTP.
Creative Biolabs offers a full range of neural research-related products and services. Please feel free to contact us for more detailed information.
- NeuroMab™ Anti-EPHB2 Antibody(NRP-0422-P1220) (Cat#: NRP-0422-P1220)
- NeuroMab™ Anti-ApoC3 BBB Shuttle Antibody(NRZP-1022-ZP3505) (Cat#: NRZP-1022-ZP3505)
- NeuroMab™ Rabbit Anti-Alpha-synuclein (CBP1631) (Cat#: NAB-08-PZ079)
- NeuroMab™ Mouse Anti-LRP1 Monoclonal Antibody (CBP3363) (Cat#: NAB-0720-Z6479)
- NeuroMab™ Anti-TREM2 Antibody(NRP-0422-P792) (Cat#: NRP-0422-P792)
- NeuroMab™ Anti-SEZ6 Antibody(NRP-0422-P517) (Cat#: NRP-0422-P517)
- NeuroMab™ Anti-GD2 Antibody(NRZP-1222-ZP767) (Cat#: NRZP-1222-ZP767)
- NeuroMab™ Mouse Anti-EFNB2 Monoclonal Antibody (CBP1159) (Cat#: NAB-0720-Z4396)
- NeuroMab™ Anti-Integrin αvβ8 BBB Shuttle Antibody(NRZP-1222-ZP1218) (Cat#: NRZP-1222-ZP1218)
- NeuroMab™ Anti-Tau Antibody(NRP-0422-P1686) (Cat#: NRP-0422-P1686)
- Rat Microglia Cell Line HAPI, Immortalized (Cat#: NCL2110P015)
- Green Fluorescent Tau SH-SY5Y cell Line (Cat#: NCL2110P219)
- Mouse Glioma Cell Line GL261-GFP (Cat#: NCL-2108P04)
- iNeu™ Human Sensory Neurons (Cat#: NCL-2103-P62)
- iNeu™ Retinal Pigment Epithelial Cells (RPE) (Cat#: NRZP-0323-ZP92)
- Rat Muller Cell (Cat#: NCL2110P040)
- iNeu™ Microglia (Cat#: NCL-7P018)
- Green Fluorescent BACE1 Cell Lines (Cat#: NCL2110P214)
- C57 Brain Cortex Neurons [Mouse] (Cat#: NCC20-9PZ48)
- Human Astrocytes, Immortalized (Cat#: NCL-2105-P182-AM)
- Amyloid beta 1-42 Kit (Cat#: NRP-0322-P2170)
- Beta Amyloid (1-40), Aggregation Kit (Cat#: NRZP-0323-ZP199)
- Alpha-Synuclein Aggregation Assay Kit (Cat#: NRZP-1122-ZP37)
- Human Tau Aggregation Kit (Cat#: NRP-0322-P2173)
- Alpha Synuclein Aggregation Kit (Cat#: NRZP-1122-ZP15)
- Human Poly ADP ribose polymerase,PARP Assay Kit (Cat#: NRZP-1122-ZP62)
- Beta Amyloid (1-42), Aggregation Kit (Cat#: NRZP-0323-ZP200)
- Human GFAP ELISA Kit [Colorimetric] (Cat#: NPP2011ZP383)
- AAV-mDLX-CRE-tdTomato (Cat#: NRZP-0622-ZP721)
- AAV2 Full Capsids, Reference Standards (Cat#: NTC2101070CR)
- pAAV-syn-jGCaMP8s-WPRE (Cat#: NTA-2106-P063)
- pAAV-syn-jGCaMP8m-WPRE (Cat#: NTA-2106-P062)
- Dextran-FITC (Cat#: NTA-2011-ZP110)
- PRV-CAG-EGFP (Cat#: NTA-2011-ZP14)
- AAV2/9-hSyn-Flpo-EGFP-WPRE-pA (Cat#: NTA-2012-ZP149)
- pAAV-EF1a-DIO-EGFP-WPRE (Cat#: NTA-2012AD-P285)
- AAV2/9-hEF1a-fDIO-eNpHR 3.0-mCherry-WPRE-pA (Cat#: NTA-2012-ZP78)
- VSV-eGFP (Cat#: NTA-2011-ZP20)
- ABCA1 Antisense Oligonucleotide (NV-2106-P27) (Cat#: NV-2106-P27)
- Human superoxide dismutase 1, soluble (SOD1) (NM_000454) ORF clone, TurboGFP Tagged (Cat#: NEP-0521-R0748)
- Mouse SOD1 shRNA Silencing Adenovirus (Cat#: NV-2106-P14)
- Tau Antisense Oligonucleotide (IONIS-MAPTRx) (Cat#: NV-2106-P29)
- App Rat amyloid beta (A4) precursor protein (App)(NM_019288) ORF clone, Untagged (Cat#: NEP-0421-R0053)
- Rat Parkinson disease (autosomal recessive, juvenile) 2, parkin (Park2) (NM_020093) ORF clone/lentiviral particle, Myc-DDK Tagged (Cat#: NEP-0621-R0041)
- Lenti of Mouse synuclein, alpha (Snca) transcript variant (NM_001042451) ORF clone, mGFP Tagged (Cat#: NEP-0521-R0864)
- Human apolipoprotein E (APOE) (NM_000041) ORF clone, Untagged (Cat#: NEP-0421-R0232)
- Human huntingtin (HTT) (NM_002111) ORF clone, Myc-DDK Tagged (Cat#: NEP-0521-R0497)
- Mouse Parkinson disease (autosomal recessive, early onset) 7 (Park7) (NM_020569) clone, Untagged (Cat#: NEP-0621-R0133)
- NeuroBiologics™ Mouse Cerebrospinal Fluid (Cat#: NRZP-0822-ZP497)
- NeuroBiologics™ Pig Cerebrospinal Fluid (Cat#: NRZP-0822-ZP498)
- NeuroBiologics™ Rat Cerebrospinal Fluid (Cat#: NRZP-0822-ZP496)
- NeuroBiologics™ Monkey Cerebrospinal Fluid (Cat#: NRZP-0822-ZP495)
- NeuroBiologics™ Human Cerebrospinal Fluid (Cat#: NRZP-0822-ZP491)
- NeuroPro™ Anti-Erythropoietin BBB Shuttle Protein (Cat#: NRZP-0423-ZP499)
- NeuroPro™ Anti-EPO BBB Shuttle Protein (Cat#: NRZP-0423-ZP508)
- NeuroPro™ Anti-TNFR BBB Shuttle Protein (Cat#: NRZP-0423-ZP510)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP500)
- NeuroPro™ Anti-NAGLU BBB Shuttle Protein (Cat#: NRZP-0423-ZP506)
- NeuroPro™ Anti-PON1 BBB Shuttle Protein (Cat#: NRZP-0423-ZP507)
- NeuroPro™ Anti-IDUA BBB Shuttle Protein (Cat#: NRZP-0423-ZP498)
- NeuroPro™ Anti-IDS BBB Shuttle Protein (Cat#: NRZP-0423-ZP503)
- NeuroPro™ Anti-GDNF BBB Shuttle Protein (Cat#: NRZP-0423-ZP509)
- NeuroPro™ Anti-IDUA BBB Shuttle Protein (Cat#: NRZP-0423-ZP502)