A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans

Spiegel, Ronen; Bach, Gideon; Sury, Vivi; Mengistu, Getu; Meidan, Bela; Shalev, Stavit; Shneor, Yona; Mandel, Hanna; Zeigler, Marsha

doi:10.1016/j.ymgme.2004.10.004

Cited by 118 publications

(83 citation statements)

References 22 publications

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“…Spiegel described the first case of saposin A deficit in a 6-month-old girl presenting with progressive encephalopathy [21]. She was diagnosed as suffering from β-galactocerebrosidase deficiency based on enzyme activity found in leukocytes isolated from the whole blood.…”

Section: B Bmentioning

confidence: 99%

Original article Diagnostic difficulties in Krabbe disease: a report of two cases and review of literature

Sztefko

Ługowska²,

Laure‐Kamionowska³

et al. 2012

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Section: B Bmentioning

confidence: 99%

Original article Diagnostic difficulties in Krabbe disease: a report of two cases and review of literature

Sztefko

Ługowska²,

Laure‐Kamionowska³

et al. 2012

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“…Sap B, or Sap C defi ciencies in humans are rare ( 181,(187)(188)(189). Sap D activates AC for degradation of ceramide.…”

Section: Downloaded Frommentioning

confidence: 99%

Multi-system disorders of glycosphingolipid and ganglioside metabolism

Xu¹,

Barnes²,

Sun³

et al. 2010

Journal of Lipid Research

142

121

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important to a variety of cellular functions. GSLs and gangliosides are synthesized at the endoplasmic reticulum (ER) and are remodeled during transit from cis to trans Golgi by a series of glycosyl-and sialyl-transferases. These are then transported to the intracellular compartments and the plasma membrane where they become enriched in microdomains and membrane bilayers. During plasma membrane turnover, GSLs and gangliosides can be internalized and partially or completely degraded in the endosomal/lysosomal system to sphingosine and free fatty acids that are then transported or fl ipped across late endosomal and lysosomal membranes for recycling or for use as signaling molecules ( 2, 3 ). GSL metabolic pathwaysGSL biosynthesis begins with condensation of serine and palmitoyl-CoA catalyzed by serine-palmitoyltransferase (SPT) on the cytoplasmic face of the ER, leading to de novo biosynthesis of ceramide, the core of GSLs (

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“…Saposin A activates the hydrolysis of galactosylceramide by β-galactosylceramidase to produce ceramide and galactose (7,8). Loss of functional saposin A results in a variant form of Krabbe disease, which is characterized by demyelination, loss of oligodendrocytes, and infiltration of globoid cells (9)(10)(11)(12). Saposin A is also important for the loading of lipid antigens onto CD1d molecules (13,14).…”

mentioning

confidence: 99%

Structure of saposin A lipoprotein discs

Popovic

Holyoake²,

Pomès³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

146

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The saposins are small, membrane-active proteins that exist in both soluble and lipid-bound states. Saposin A has roles in sphingolipid catabolism and transport and is required for the breakdown of galactosylceramide by β-galactosylceramidase. In the absence of lipid, saposin A adopts a closed monomeric apo conformation typical of this family. To study a lipid-bound state of this protein, we determined the crystal structure of saposin A in the presence of detergent to 1.9 Å resolution. The structure reveals two chains of saposin A in an open conformation encapsulating 40 internally bound detergent molecules organized in a highly ordered bilayerlike hydrophobic core. The complex provides a high-resolution view of a discoidal lipoprotein particle in which all of the internalized acyl chains are resolved. Saposin A lipoprotein discs exhibit limited selectivity with respect to the incorporated lipid, and can solubilize phospholipids, sphingolipids, and cholesterol into discrete, monodisperse particles with mass of approximately 27 kDa. These discs may be the smallest possible lipoprotein structures that are stabilized by lipid self-assembly.protein-lipid complex | X-ray crystallography | molecular dynamics | Krabbe disease

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A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: first report of saposin A deficiency in humans

Cited by 118 publications

References 22 publications

Original article Diagnostic difficulties in Krabbe disease: a report of two cases and review of literature

Original article Diagnostic difficulties in Krabbe disease: a report of two cases and review of literature

Multi-system disorders of glycosphingolipid and ganglioside metabolism

Structure of saposin A lipoprotein discs

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