A mutation within the saposin D domain in a Gaucher disease patient with normal glucocerebrosidase activity

Dı́az-Font, Anna; Cormand, Bru; Santamaría, Ramón I.; Vilageliu, Lluı̈sa; Grinberg, Daniel; Chabás, Amparo

doi:10.1007/s00439-005-1288-x

Cited by 42 publications

(23 citation statements)

References 7 publications

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“…A primary function of saposin D is to enhance the hydrolysis of ceramide (Azuma et al, 1994), and thus saposin D deficiency leads to ceramide accumulation, most prominently in the cerebellum (Matsuda et al, 2004). Saposin D deficiency has also been reported in a patient diagnosed with Gaucher’s disease (Diaz-Font et al, 2005). Interestingly, total saposin deficiency results in a phenotype that is much more severe than the phenotypes observed upon loss of the individual saposins (Fujita et al, 1996; Hulkova et al, 2001), which suggests that full-length prosaposin possesses biological activities above and beyond the enzymatic actions exhibited by the individual saposins.…”

Section: The Function Of Prosaposin and The Saposinsmentioning

confidence: 93%

The protective role of prosaposin and its receptors in the nervous system

et al. 2014

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Prosaposin (also known as SGP-1) is an intriguing multifunctional protein that plays roles both intracellularly, as a regulator of lysosomal enzyme function, and extracellularly, as a secreted factor with neuroprotective and glioprotective effects. Following secretion, prosaposin can undergo endocytosis via an interaction with the low-density lipoprotein-related receptor 1 (LRP1). The ability of secreted prosaposin to promote protective effects in the nervous system is known to involve activation of G proteins, and the orphan G protein-coupled receptors GPR37 and GPR37L1 have recently been shown to mediate signaling induced by both prosaposin and a fragment of prosaposin known as prosaptide. In this review, we describe recent advances in our understanding of prosaposin, its receptors and their importance in the nervous system.

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Section: The Function Of Prosaposin and The Saposinsmentioning

confidence: 93%

The protective role of prosaposin and its receptors in the nervous system

et al. 2014

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“…Six patients with Sap C deficiency due to mutations in the PSAP gene have been reported in the literature, all of whom had symptoms resembling GD [9,77–83]. Two of these patients exhibited a type 1 GD phenotype, while two had neurological involvement resembling type 3 GD [9,77,80].…”

Section: Clinical Consequences Of Saposin C Deficiencymentioning

confidence: 99%

The role of saposin C in Gaucher disease

Tamargo

Velayati

Goldin

et al. 2012

Molecular Genetics and Metabolism

107

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Saposin C is one of four homologous proteins derived from sequential cleavage of the saposin precursor protein, prosaposin. It is an essential activator for glucocerebrosidase, the enzyme deficient in Gaucher disease. Gaucher disease is a rare autosomal recessive lysosomal storage disorder caused by mutations in the GBA gene that exhibits vast phenotypic heterogeneity, despite its designation as a “simple” Mendelian disorder. The observed phenotypic variability has led to a search for disease modifiers that can alter the Gaucher phenotype. The PSAP gene encoding saposin C is a prime candidate modifier for Gaucher disease. In humans, saposin C deficiency due tomutations in PSAP results in a Gaucher-like phenotype, despite normal in vitro glucocerebrosidase activity. Saposin C deficiency has also been shown to modify phenotype in one mousemodel of Gaucher disease. The role of saposin C as an activator required for normal glucocerebrosidase function, and the consequences of saposin C deficiency are described, and are being explored as potential modifying factors in patients with Gaucher disease.

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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.…”

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confidence: 99%

“…Sap D activates AC for degradation of ceramide. Heteroallelic mutations were identifi ed in the Sap D domain in a patient with an additional mutation in the Sap C domain on a different allele ( 189 ). Prosaposin and all four Sap-defi cient mice have been developed ( 98,(190)(191)(192)(193)(194).…”

Section: Downloaded Frommentioning

confidence: 99%

Multi-system disorders of glycosphingolipid and ganglioside metabolism

Xu¹,

Barnes²,

Sun³

et al. 2010

Journal of Lipid Research

140

120

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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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A mutation within the saposin D domain in a Gaucher disease patient with normal glucocerebrosidase activity

Cited by 42 publications

References 7 publications

The protective role of prosaposin and its receptors in the nervous system

The protective role of prosaposin and its receptors in the nervous system

The role of saposin C in Gaucher disease

Multi-system disorders of glycosphingolipid and ganglioside metabolism

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