Specificity of low molecular weight glycoprotein effector of lipid glycosidase

Ho, Mae‐Wan

doi:10.1016/0014-5793(75)80029-9

Cited by 47 publications

(8 citation statements)

References 11 publications

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“…The association of the proteins and hydrolase activation is recovered when lipids, especially negatively charged lipids, are added (30)(31)(32)(33). [Earlier GCase preparations were shown to bind Sepharose-coupled sapC (34,35), and sapC induced the lowering of the GCase K m value for 4-methylumbelliferyl-␤-D-glucopyranoside (MUG) hydrolysis (35). However, the same preparations were shown to contain considerable amounts of lipids (35).]…”

Section: Discussionmentioning

confidence: 99%

Molecular imaging of membrane interfaces reveals mode of β-glucosidase activation by saposin C

Alattia

Shaw²,

Yip³

et al. 2007

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

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Acid ␤-glucosidase (GCase) is a soluble lysosomal enzyme responsible for the hydrolysis of glucose from glucosylceramide and requires activation by the small nonenzymatic protein saposin C (sapC) to gain access to the membrane-embedded glycosphingolipid substrate. We have used in situ atomic force microscopy (AFM) with simultaneous confocal and epifluorescence microscopies to investigate the interactions of GCase and sapC with lipid bilayers. GCase binds to sites on membranes transformed by sapC, and enzyme activity occurs at loci containing both GCase and sapC. Using FRET, we establish the presence of GCase/sapC and GCase/ product contacts in the bilayer. These data support a mechanism in which sapC locally alters regions of bilayer for subsequent attack by the enzyme in stably bound protein complexes.atomic force microscopy ͉ confocal microscopy ͉ FRET ͉ interfacial catalysis ͉ lipid storage disease

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Section: Discussionmentioning

confidence: 99%

Molecular imaging of membrane interfaces reveals mode of β-glucosidase activation by saposin C

Alattia

Shaw²,

Yip³

et al. 2007

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

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“…SAP-C is thought to stimulate ␤-GlcCerase by an allosteric mechanism, resulting in trimeric complex formation between the water-soluble enzyme, the activator protein, and the membrane-associated glycolipid (1,7). In vitro data have demonstrated the ability of SAP-C to form complexes with ␤-GlcCerase in the presence of phosphatidylserine (32,33). However, in vivo binding of SAP-C to GlcCers may also contribute to the stimulation of GlcCer hydrolysis.…”

Section: Discussionmentioning

confidence: 99%

Sphingolipid Activator Proteins Are Required for Epidermal Permeability Barrier Formation

Doering

Holleran

Potratz

et al. 1999

Journal of Biological Chemistry

143

112

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The epidermal permeability barrier is maintained by extracellular lipid membranes within the interstices of the stratum corneum. Ceramides, the major components of these multilayered membranes, derive in large part from hydrolysis of glucosylceramides mediated by stratum corneum ␤-glucocerebrosidase (␤-GlcCerase). Prosaposin (pSAP) is a large precursor protein that is proteolytically cleaved to form four distinct sphingolipid activator proteins, which stimulate enzymatic hydrolysis of sphingolipids, including glucosylceramide. Recently, pSAP has been eliminated in a mouse model using targeted deletion and homologous recombination. In addition to the extracutaneous findings noted previously, our present data indicate that pSAP deficiency in the epidermis has significant consequences including: 1) an accumulation of epidermal glucosylceramides together with below normal levels of ceramides; 2) alterations in lipids that are bound by ester linkages to proteins of the cornified cell envelope; 3) a thickened stratum lucidum with evidence of scaling; and 4) a striking abnormality in lamellar membrane maturation within the interstices of the stratum corneum. Together, these results demonstrate that the production of pSAP, and presumably mature sphingolipid activator protein generation, is required for normal epidermal barrier formation and function. Moreover, detection of significant amounts of covalently bound -OH-GlcCer in pSAP-deficient epidermis suggests that deglucosylation to -OH-Cer is not a requisite step prior to covalent attachment of lipid to cornified envelope proteins.

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“…Unlike GMZactivator and sup-B, sup-C is reported to form complexes with membrane-associated enzymes and apparently activates them [38][39][40][41].…”

Section: Topology and Mechanism Of Lysosomal Glycolipid Degradation Rmentioning

confidence: 99%

Intracellular trafficking of glycosphingolipids: Role of sphingolipid activator proteins in the topology of endocytosis and lysosomal digestion

Sandhoff

Klein

1994

FEBS Letters

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Glycosphingolipids (GSL) are components of the outer leaflet of the plasma membrane (PM) of vertebrate tissues. Our current knowledge of GSL metabolism and their intracellular traffic has been derived from metabolic studies but the exact mechanisms by which GSLs are transported from sites of synthesis (endoplasmic reticulum and Golgi) to the sites of residence (PM) and degradation (lysosomes) have not been clearly defined. It is now established that components of the PM reach the lysosomal compartment mainly by endocytic membrane flow. According to a new model, GSLs derived from the PM are thought to end up in intra-endosomal vesicles which could be delivered, by successive processes of membrane fission and fusion, along the endocytic pathway directly into the lumen of the lysosomes. Here the GSLs are degraded in a step-wise manner by exohydrolases. However, the catabolism of membrane-bound GSLs with short hydrophilic head groups needs the assistance of sphingolipid activator proteins (SAPS), which lift the GSLs from the plane of the membrane and present them for degradation to the lysosomal exohydrolases, which are usually water-soluble. The inherited deficiency of one of these enzymes or SAPS causes the lysosomal storage of their respective GSL substrates. In the case of the simultaneous deficiency of all 4 different SAPS the storage of all GSLs with short hydrophilic head groups occurs within multivesicular bodies and/or intra-lysosomal vesicles.

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Specificity of low molecular weight glycoprotein effector of lipid glycosidase

Cited by 47 publications

References 11 publications

Molecular imaging of membrane interfaces reveals mode of β-glucosidase activation by saposin C

Molecular imaging of membrane interfaces reveals mode of β-glucosidase activation by saposin C

Sphingolipid Activator Proteins Are Required for Epidermal Permeability Barrier Formation

Intracellular trafficking of glycosphingolipids: Role of sphingolipid activator proteins in the topology of endocytosis and lysosomal digestion

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