Abstract
Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed 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—the 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, result 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 the 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3325-3336 |
| Number of pages | 12 |
| Journal | Journal of Molecular Biology |
| Volume | 428 |
| Issue number | 16 |
| DOIs | |
| State | Published - Aug 14 2016 |
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Keywords
- glycan binding protein
- glycosphingolipid
- lipid raft
- receptor tyrosine kinase
- sialic acid
ASJC Scopus subject areas
- Medicine(all)
- Molecular Biology
Cite this
Gangliosides of the Vertebrate Nervous System. / Schnaar, Ronald Lee.
In: Journal of Molecular Biology, Vol. 428, No. 16, 14.08.2016, p. 3325-3336.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Gangliosides of the Vertebrate Nervous System
AU - Schnaar, Ronald Lee
PY - 2016/8/14
Y1 - 2016/8/14
N2 - Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed 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—the 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, result 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 the 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.
AB - Gangliosides, sialylated glycosphingolipids, found on all vertebrate cells and tissues, are major molecular determinants on the surfaces of vertebrate nerve cells. Composed 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—the 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, result 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 the 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.
KW - glycan binding protein
KW - glycosphingolipid
KW - lipid raft
KW - receptor tyrosine kinase
KW - sialic acid
UR - http://www.scopus.com/inward/record.url?scp=84982062283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84982062283&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2016.05.020
DO - 10.1016/j.jmb.2016.05.020
M3 - Review article
VL - 428
SP - 3325
EP - 3336
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 16
ER -