Ganglioside Regulation of AMPA Receptor Trafficking

Prendergast, Jillian; Umanah, George K.E.; Yoo, Seung Wan; Lagerlöf, Olof; Motari, Mary G.; Cole, Robert N.; Huganir, Richard L.; Dawson, Ted M.; Dawson, Valina L.; Schnaar, Ronald L.

doi:10.1523/jneurosci.1149-14.2014

Cited by 53 publications

(33 citation statements)

References 55 publications

(1 reference statement)

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“…These results indicate that ceramide is not modulating AMPAR expression itself but might be necessary for other mechanisms in spinogenesis. In fact, other studies have described the involvement of GM1 ganglioside (a ceramide derivative) in the regulation of GluA2-containing AMPAR synaptic content by acting on endocytosis (46). In summary, our results demonstrate that CPT1C is necessary for an efficient translation of AMPARs.…”

Section: Cpt1csupporting

confidence: 69%

Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus

Fadó

Soto

Miñano-Molina

et al. 2015

Journal of Biological Chemistry

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Background:One interacting partner of the AMPA receptor (AMPAR) complex in the endoplasmic reticulum is carnitine palmitoyltransferase 1C (CPT1C). Results: CPT1C regulates synaptic AMPAR levels and synaptic transmission by post-transcriptional regulation of GluA1 protein synthesis. Conclusion: CPT1C is a new regulator of AMPAR translation efficiency. Significance: CPT1C modulation could be a new tool to prevent AMPAR decline and learning deficits.

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Section: Cpt1csupporting

confidence: 69%

Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus

Fadó

Soto

Miñano-Molina

et al. 2015

Journal of Biological Chemistry

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“…It has been reported that the activation of AMPA receptors increases the expression of several isoforms of gangliosides in the hippocampus [ 24 ]. Gangliosides have the ability to regulate the function of the AMPA receptor [ 25 ]. Similarly, the association between phospholipids and glutamate trafficking has also been reported, for example the ability of phosphatidylinositol in maintaining glutamate synaptic trafficking [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Supplementation with Beta Serum Concentrate (BSC), a Complex of Milk Lipids, during Post-Natal Brain Development Improves Memory in Rats

et al. 2015

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We have previously reported that the supplementation of ganglioside-enriched complex-milk-lipids improves cognitive function and that a phospholipid-enriched complex-milk-lipid prevents age-related cognitive decline in rats. This current study evaluated the effects of post-natal supplementation of ganglioside- and phospholipid-enriched complex-milk-lipids beta serum concentrate (BSC) on cognitive function in young rats. The diet of male rats was supplemented with either gels formulated BSC (n = 16) or blank gels (n = 16) from post-natal day 10 to day 70. Memory and anxiety-like behaviors were evaluated using the Morris water maze, dark–light boxes, and elevated plus maze tests. Neuroplasticity and white matter were measured using immunohistochemical staining. The overall performance in seven-day acquisition trials was similar between the groups. Compared with the control group, BSC supplementation reduced the latency to the platform during day one of the acquisition tests. Supplementation improved memory by showing reduced latency and improved path efficiency to the platform quadrant, and smaller initial heading error from the platform zone. Supplemented rats showed an increase in striatal dopamine terminals and hippocampal glutamate receptors. Thus BSC supplementation during post-natal brain development improved learning and memory, independent from anxiety. The moderately enhanced neuroplasticity in dopamine and glutamate may be biological changes underlying the improved cognitive function.

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“…An unbiased screen for nerve cell proteins that differentially bind to gangliosides GT1b and GM1 revealed a group of proteins that regulate the intracellular trafficking of the GluR2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type glutamate receptor, the major excitatory neurotransmitter receptor in the brain [75]. AMPA receptors are tetrameric transmembrane proteins composed of dimers of dimers constructed from four gene products (GluR1-GluR4), the most common being GluR1-GluR2 and GluR2-GluR3 [76].…”

Section: Functions Of Nervous System Gangliosides In Health and Diseasementioning

confidence: 99%

Gangliosides of the Vertebrate Nervous System

Schnaar

2016

Journal of Molecular Biology

166

143

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Gangliosides, sialylated glycosphingolipids found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Comprised of a sialylated glycan attached to a ceramide lipid, the same four structures – GM1, GD1a, GD1b and GT1b – represent the vast majority (>90%) of gangliosides in the brains of all mammals and birds. Primarily found on the outer surface of the plasma membrane with their glycans facing outward, gangliosides associate laterally with each other, sphingomyelin, cholesterol, and select proteins in lipid rafts – dynamic functional subdomains of the plasma membrane. The functions of gangliosides in the human nervous system are revealed by congenital mutations in ganglioside biosynthetic genes. Mutations in ST3GAL5, which codes for an enzyme early in brain ganglioside biosynthesis, results in an early-onset seizure disorder with profound motor and cognitive decay, whereas mutations in B4GALNT1, a gene encoding a later step, result in hereditary spastic paraplegia accompanied by intellectual deficits. The molecular functions of brain gangliosides include regulation of receptors in the same membrane via lateral (cis) associations and regulation of cell-cell recognition by trans interaction with ganglioside binding proteins on apposing cells. Gangliosides also affect aggregation of Aβ (Alzheimer’s disease) and α-synuclein (Parkinson’s Disease). As analytical, biochemical and genetic tools advance, research on gangliosides promises to reveal mechanisms of molecular control related to nerve and glial cell differentiation, neuronal excitability, axon outgrowth after nervous system injury, and protein folding in neurodegenerative diseases.

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Ganglioside Regulation of AMPA Receptor Trafficking

Cited by 53 publications

References 55 publications

Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus

Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus

Long-Term Supplementation with Beta Serum Concentrate (BSC), a Complex of Milk Lipids, during Post-Natal Brain Development Improves Memory in Rats

Gangliosides of the Vertebrate Nervous System

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