Background
Classification of ADCYs
Mammalian ADCYs
Gene name | Chromosome (human) | Chromosome (mouse) | Structure | Length (human) | Length (mouse) |
---|---|---|---|---|---|
ADCY1 | 7p12 | 11A2 | 1119 | 1118 | |
ADCY2 | 5p15 | 13C1 | 1091 | 1090 | |
ADCY3 | 2p22-24 | 12A-B | 1144 | 1145 | |
ADCY4 | 14q11.2 | 14D3 | 1077 | 1077 | |
ADCY5 | 3q13.2-q21 | 16B5 | 1261 | 1262 | |
ADCY6 | 12q12-13 | 15F | 1168 | 1165 | |
ADCY7 | 16q12-13 | 8C3-D | 1080 | 1099 | |
ADCY8 | 8q24 | 15 | 1251 | 1249 | |
ADCY9 | 16p13.3 | 16B1 | 1353 | 1353 | |
ADCY10 | 1q24.2 | 1 | 1610 | 1614 |
Regulation of ADCYs
Group I
Group II
Group III
Group IV
sADCY/ADCY10
Expression and functions of ADCYs in the CNS
Isoforms | Sites of expression | Cell types |
---|---|---|
ADCY1 | Piriform cortex#, CA1-CA2 of hippocampus#, dentate gyrus#, striatum#, amygdala^, thalamus#, and cerebellum#, cerebral cortex^, and olfactory bulb layers* | Neurons#, oligodendrocytes^, microglia^, astrocytes^, fibroblasts* and endothelial cells* |
ADCY2 | Piriform cortex#, CA1 of hippocampus#, dentate gyrus#, striatum#, CA2-CA3 of hippocampus^, thalamus^, hypothalamus^, olfactory bulb layers^, cerebral cortex^, amygdala*, and cerebellum* | Neurons#, astrocytes#, fibroblasts#, smooth muscle cells#, oligodendrocytes^, microglia*, endothelial cells*, pericytes* |
ADCY3 | CA1-CA3 of hippocampus#, dentate gyrus#, cerebral cortex^, striatum^, amygdala^, thalamus^, hypothalamus^, cerebellum^, olfactory bulb layers*, piriform cortex*, and choroid plexus | Neurons#, astrocytes#, fibroblasts#, pericytes#, oligodendrocytes^, smooth muscle cells*, microglia*, endothelial cells*, and choroid plexus epithelial cells |
ADCY4 | Hippocampus* and olfactory epithelium* | Endothelial cells#, neurons*, astrocytes*, fibroblasts*, smooth muscle cells*, oligodendrocytes*, microglia*, and pericytes* |
ADCY5 | Striatum#, hypothalamus^, olfactory bulb layers^, cerebral cortex*, piriform cortex*, amygdala*, CA1-CA3 of hippocampus*, dentate gyrus*, and thalamus* | Neurons#, oligodendrocytes#, fibroblasts#, smooth muscle cells#, astrocytes*, microglia*, endothelial cells*, and pericytes* |
ADCY6 | Piriform cortex#, amygdala#, CA1-CA3 of hippocampus#, dentate gyrus#, hypothalamus#, cerebellum#, choroid plexus#, olfactory bulb layers^, cerebral cortex^, striatum^, and thalamus^ | Neurons#, astrocytes#, fibroblasts#, smooth muscle cells#, oligodendrocytes#, endothelial cells#, pericytes#, and microglia* |
ADCY7 | Thalamus^, and hypothalamus^, cerebral cortex*, amygdala*, corpus callosum*, cerebellum*, and olfactory system* | Fibroblasts#, smooth muscle cells#, microglia#, neurons*, astrocytes*, oligodendrocytes*, endothelial cells*, and pericytes* |
ADCY8 | Piriform cortex#, CA1-CA2 of hippocampus#, dentate gyrus#, thalamus#, hypothalamus#, cerebellum#, olfactory bulb#, cerebral cortex*, and amygdala* | Neurons#, astrocytes#, fibroblasts*, smooth muscle cells*, oligodendrocytes*, microglia*, and endothelial cells* |
ADCY9 | Olfactory bulb#, cerebral cortex#, piriform cortex#, CA1-CA3 of hippocampus#, dentate gyrus#, cerebellum#, amygdala^, thalamus*, and hypothalamus* | Neurons#, astrocytes#, fibroblasts#, smooth muscle cells#, oligodendrocytes#, microglia#, endothelial cells#, and pericytes# |
ADCY10 | Visual cortex*, hippocampus*, and cerebellum*, and choroid plexus | Neurons*, astrocytes*, fibroblasts*, smooth muscle cells*, oligodendrocytes*, microglia*, endothelial cells*, pericytes*, and choroid plexus epithelial cells |
Isoforms | Knockout/knockdown | Overexpression | Potential functions | Associated diseases | References |
---|---|---|---|---|---|
ADCY1 | Yesa | Yes | Learning, memory, LTP, synaptic plasticity, drug dependency, nociception, and pain | Anxiety-like behavior, hearing impairment, sleep deprivation, schizophrenia, bipolar disorder, and autism | |
ADCY2 | – | – | Synaptic plasticity and neuropsychiatric functions | Bipolar disorder, anxiety, stress-like disorders, Lesch-Nyhan disease, and schizophrenia | |
ADCY3 | Yesa,b | – | Odorant signaling, learning, and memory | Obesity, depression, and inflammatory bowel disease | |
ADCY4 | Yesb | – | – | – | [81] |
ADCY5 | Yesa,c | Yes | Learning, memory, synaptic plasticity, and extrapyramidal motor functions | Familial dyskinesia and facial myokymia, anxiety, depressive-like disorder, and movement disorders | |
ADCY6 | Yesa | Yes | Metabolic functions and fluid homeostasis in kidney | Axoglial diseases and lethal congenital contracture syndrome | |
ADCY7 | Yesc | Yes | Alcohol dependency | Depression-like disorder, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, and autoimmune diseases | |
ADCY8 | Yesa | Yes | Learning, memory, LTP, synaptic plasticity, nociception, and pain | Dissociative amnesia, post-traumatic stress disorder, depression, and bipolar disorder | |
ADCY9 | Yesa | Yes | Learning and memory, immunological functions, and cardioprotective | Asthma, mood disorders, and bipolar disorder | |
ADCY10 | Yesa | – | Synaptic plasticity, learning and memory, ocular dominance plasticity, and fertilization | Infertility and absorptive hypercalciuria |
ADCY1
Expression
Function
ADCY2
Expression
Function
ADCY3
Expression
Function
ADCY4
Expression
Function
ADCY5
Expression
Function
ADCY6
Expression
Function
ADCY7
Expression
Function
ADCY8
Expression
Function
ADCY9
Expression
Function
ADCY10
Expression
Function
Effects of GPCR-ADCY signaling in BBB integrity
GPCRs | Types of G proteins | BBB integrity | Cell types | References |
---|---|---|---|---|
S1PR1 | Gαi/o | Increase | Astrocytes and endothelial cells | |
S1PR2 | Gαi/o, Gαq/11, and Gα12/13 | Decrease | Pericytes, glia, fibroblasts, and endothelial cells | |
S1PR3 | Gαi/o, Gαq/11, and Gα12/13 | Decrease | Astrocytes and endothelial cells | |
S1PR5 | Gαi/o and Gα12/13 | Increase | Oligodendrocytes and endothelial cells | |
LAPR1 | Gαi/o, Gαq/11, and Gα12/13 | Decrease | Microglia, oligodendrocytes, astrocytes, and endothelial cells | |
LAPR2 | Gαi/o, Gαq/11, and Gα12/13 | Decrease | Neuron, fetal astrocytes, and endothelial cells | |
LAPR3 | Gαi/o and Gαq/11 | Decrease | Microglia, astrocytes, and endothelial cells | |
LAPR6 | Gαs and Gα12/13 | Decrease | Microglia, oligodendrocytes, and endothelial cells | |
CB1 | Gαs, Gαi/o, and Gαq | Increase | Microglia and neurons | |
CB2 | Gαs, Gαi/o, and Gαq | Increase | Microglia and neurons | |
AR-A1 | Gαi/o | Decrease | Microglia, neurons, oligodendrocytes, astrocytes, and endothelial cells | |
AR-A2A | Gαs | Decrease | Microglia, neurons, and astrocytes | |
GPER-1 | Gαs and Gβγ | Increase | Neurons | |
C5aR | Gαi/o | Decrease | Microglia, astrocytes, and neurons | |
SSTRs | Gαi/o and Gβγ | Increase | Neurons | |
GLP1R | Gαs | Increase | Microglia, astrocytes, neurons, and endothelial cells | |
HCAR1 | Gαi/o | Increase | Astrocytes, neurons, and endothelial cells |