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Literature summary for 3.1.1.116 extracted from

  • Keimpema, E.; Alpar, A.; Howell, F.; Malenczyk, K.; Hobbs, C.; Hurd, Y.; Watanabe, M.; Sakimura, K.; Kano, M.; Doherty, P.; Harkany, T.
    Diacylglycerol lipase alpha manipulation reveals developmental roles for intercellular endocannabinoid signaling (2013), Sci. Rep., 3, 2093 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.1.116

Cloned(Commentary)

Cloned (Comment) Organism
gene Dagla, stable functional overexpression of V5-tagged DAGLalpha in COS-7 cell membranes, no DAGLalpha-induced change in COS-7 cell morphology or density is observed Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information construction of DAGLalpha knockout mice. Cholinergic innervation of CA1 pyramidal cells of the hippocampus is sensitive to the genetic disruption of 2-arachidonoylglycerol (2-AG) signaling in DAGLalpha null mice. A hybrid COS-7-cholinergic neuron co-culture system demonstrates that heterologous DAGLalpha overexpression spherically excludes cholinergic growth cones from 2-AG-rich extracellular environments, and minimizes cell-cell contact in vitro. CB1R-mediated exclusion responses lasts 3 days, indicating sustained spherical 2-AG availability. Extracellular 2-AG concentrations can be sufficient to activate CB1Rs along discrete spherical boundaries to modulate neuronal responsiveness. When co-culturing cholinergic neurons and COS-7-DAGLalpha cells for 1-3 days in vitro (DIV), parent COS-7 cells attract cholinergic neurites, which course on or along COS-7 plasmalemmas already by 1 DIV. Accordingly, the distance between cholinergic GCs and the opposing membrane of COS-7 cells gradually decreases as a factor of time. In contrast, 55.0% of cholinergic GCs are prevented from approaching the proximal COS-7 cell's plasmalemma upon DAGLalpha overexpression by 3 DIV. DAGLalpha overexpression spherically excludes cholinergic GCs, as reflected by their significantly increased distance to the surface of COS-7-DAGLalpha cells. DAGLalpha overexpression does not affect the angle at which GCs approach COS-7-DAGLalpha cells, the length of cholinergic neurites, the distance between cholinergic and COS-7 somata, and the survival of p75NTR1 neurons in vitro, excluding delayed morphogenesis or neuronal migration as confounding factors. Yet DAGLalpha overexpression no longer affects neurite growth, confining endocannabinoid action to affecting GC motility but no other forms of e.g. contact guidance. Focal and extracellular 2-AG can alter the positioning of cholinergic GCs. DAGLalpha overexpression in COS-7 cells is the only variable that contributes to the phenomena, supporting a role for intercellular 2-AG signaling Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
plasma membrane isozyme DAGLalpha is a protein with four trans-membrane domains Mus musculus 5886
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synapse
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 Mus musculus 45202
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Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O Mus musculus
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 2-arachidonoylglycerol + fatty acid
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 ?

Organism

Organism UniProt Comment Textmining
Mus musculus Q6WQJ1
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Source Tissue

Source Tissue Comment Organism Textmining
brain fetal cholinergic basal forebrain Mus musculus
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forebrain
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 Mus musculus
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hippocampus fetal, neonatal, and adult Mus musculus
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additional information 2-arachidonoylglycerol (2-AG) signaling during fetal development and in adulthood, overview Mus musculus
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neuron
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 Mus musculus
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pyramidal neuron
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 Mus musculus
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1-acyl-2-arachidonoyl-sn-glycerol + H2O
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 Mus musculus 2-arachidonoylglycerol + fatty acid
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 ?

Synonyms

Synonyms Comment Organism
DAGLalpha
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 Mus musculus
diacylglycerol lipase alpha
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 Mus musculus

General Information

General Information Comment Organism
malfunction cholinergic innervation of CA1 pyramidal cells of the hippocampus is sensitive to the genetic disruption of 2-arachidonoylglycerol (2-AG) signaling in DAGLalpha null mice. Heterologous DAGLalpha overexpression spherically excludes cholinergic growth cones from 2-AG-rich extracellular environments, and minimizes cell-cell contact in vitro. Extracellular 2-AG concentrations can be sufficient to activate CB1Rs along discrete spherical boundaries to modulate neuronal responsiveness. The cholinergic phenotype brought about by DAGLalpha deletion exceeds that in DAGLbeta-/- mice, in which alterations to cholinergic synapse distribution are milder and more stochastic, precluding statistical significance. The overall density and average size of ChAT1 boutons remains unchanged Mus musculus
physiological function endocannabinoids are small signaling lipids, with 2-arachidonoylglycerol (2-AG) implicated in modulating axonal growth and synaptic plasticity, concept of short-range extracellular signaling by endocannabinoids. Endocannabinoids, particularly 2-arachidonoylglycerol (2-AG) and anandamide (AEA), modulate synaptic neurotransmission by acting on molecularly diverse cannabinoid receptors in the brain. 2-AG is chiefly recognized as the retrograde messenger engaging presynaptic CB1 cannabinoid receptors (CB1Rs) to scale neurotransmitter release. Focusing on 2-AG signaling, the molecular architecture of endocannabinoid signaling during neurodevelopment is profoundly different from that in adult brain. Primary reliance of nervous system organization and function on DAGLalpha, 2-AG signaling is required for the spatial organization, rather than synaptogenesis per se, of cholinergic hippocampal projections. CB1Rs modulate GC motility and directional growth around DAGLalpha hot spots in vitro Mus musculus