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Literature summary for 2.8.2.11 extracted from

  • Palavicini, J.P.; Wang, C.; Chen, L.; Ahmar, S.; Higuera, J.D.; Dupree, J.L.; Han, X.
    Novel molecular insights into the critical role of sulfatide in myelin maintenance/function (2016), J. Neurochem., 139, 40-54 .
    View publication on PubMedView publication on EuropePMC
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Protein Variants

Protein Variants Comment Organism
additional information a sulfatide (ST)-deficient mouse model is generated by disrupting the gene that encodes the enzyme cerebroside sulfotransferase (CST) that catalyzes the last step of ST biosynthesis. CST knockout (CST-/-) mice, which show a complete loss of ST in brain tissue, are born healthy, but begin displaying hindlimb weakness and tremors by 4-6 weeks of age. These defects aggravate with age, causing pronounced tremor and eventual ataxia, that lead to partial or complete paralysis by 12 months of age and eventually result in premature death which typically occurs around 15 months. Molecular fingerprints underlying the myelin phenotypes are described for CST KO mice, including (1) a one-third loss of compact-myelin proteins and major myelin lipids, presumably due to the loss of negative charges from ST species, (2) a striking post-developmental loss of MAG and NF155, and (3) a progressive loss of intermolecular PLP interactions. The tremor and ataxic phenotypes that occur in the absence of ST are a consequence of the loss of NF155 and PLP intermolecular interactions. Loss of ST results in reduced GalCer synthesis and/or increased GalCer degradation. ST depletion leads to a post-developmental disruption of myelin sphingolipid homeostasis. ST depletion leads to a dramatic and progressive loss of NF155 in every CNS region analyzed Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3'-phosphoadenylyl sulfate + a galactosylceramide Mus musculus
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 adenosine 3',5'-bisphosphate + a galactosylceramidesulfate
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 ?

Organism

Organism UniProt Comment Textmining
Mus musculus Q9JHE4
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-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
 Mus musculus
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myelin sheath
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 Mus musculus
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spinal cord
-
 Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3'-phosphoadenylyl sulfate + a galactosylceramide
-
 Mus musculus adenosine 3',5'-bisphosphate + a galactosylceramidesulfate
-
 ?

Synonyms

Synonyms Comment Organism
cerebroside sulfotransferase
-
 Mus musculus
CST
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 Mus musculus
Gal3st1
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 Mus musculus

General Information

General Information Comment Organism
malfunction CST knockout (CST-/-) mice, in which sulfatide is completely depleted, are born healthy, but display myelin abnormalities and progressive tremors starting at 4-6 weeks of age. A one-third reduction of the major compact-myelin proteins (myelin basic protein, MBP, and proteolipid protein, PLP) and an equivalent post-developmental loss of myelin lipids is detected, providing the molecular basis behind the thinner myelin sheaths. Lipidomics data demonstrate that the observed global reduction of myelin lipid content is not due to an increase of lipid degradation but rather to the reduction of their synthesis by oligodendrocytes. Sulfatide depletion leads to region-specific effects on non-compact myelin, dramatically affecting the paranode (neurofascin 155) and the major inner-tongue myelin protein (myelin-associated glycoprotein). Progressive decline of high molecular weight PLP complexes in CST-/- mice. Loss of ST results in reduced GalCer synthesis and/or increased GalCer degradation. Proposed molecular mechanisms underlying the effects of ST depletion on myelin structure/function, overview Mus musculus
additional information analysis of the major CNS myelin proteins and the major lipids enriched in the myelin in a spatiotemporal manner, overview Mus musculus
physiological function cerebroside sulfotransferase (CST) catalyzes the production of sulfatide, a major class of myelin-specific lipids. Sulfatide plays a critical role in myelin maintenance/function. Sulfatide (ST) promotes the interaction between adjacent PLP extracellular domains. The myelin sheath is a multilamellar, spirally wrapping extension of the plasma membrane of oligodendrocytes (OLs) in the central nervous system (CNS). Sulfatide mediates intraperiod line and myelin-axon junction interactions, and it plays a critical role in maintaining compact myelin, nodal and paranodal homeostasis Mus musculus