Structure and Function of GPI-Specific Phospholipases

Low, Martin G.

doi:10.1016/b978-012772940-4/50012-8

Cited by 12 publications

(13 citation statements)

References 113 publications

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“…Post-testicular acquisition of certain GPI-APs by spermatozoa (that normally do not synthesize these proteins) has been speculated to occur via intercellular transfer from cells of the male genital tract [124]. GPI-APs can also be released from the plasma membrane by the action of endogenous hydrolases including PI-PLC, PI-specific phospholipase D (PI-PLD), and GPIspecific PLC [125] in both lower and higher eukaryotes 1974 S. Chatterjee and S. Mayor GPI anchor and protein sorting [126,127]. In T. cruzi, PI-PLC-mediated release of GPIanchored proteins, SSp-4, and the polymorphic family of trans-sialidase/sialidases has been observed [128 -130].…”

Section: Functions Of the Gpi-anchor: A Surveymentioning

confidence: 99%

“…GPI-PLC-mediated release of VSG in trypanosomes has also been reported [133]. Such a release may be vital to rapidly switch the surface expression of VSG (several variants of which are expressed by trypanosomes [97]) to escape immune attack [125]. Studies in some higher eukaryotes have shown that the soluble form of GPI-anchored 5¢-nucleotidase present in membrane extracts of the electric organ of Torpedo marmorata (electric ray) and bovine cerebral cortex is due to the release of the protein by a PI-specific phospholipase C (PI-PLC) [127].…”

Section: Functions Of the Gpi-anchor: A Surveymentioning

confidence: 99%

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The GPI-anchor and protein sorting

Chatterjee¹,

Mayor²

2001

CMLS, Cell. Mol. Life Sci.

170

126

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Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a diverse class of proteins that are anchored to the membrane solely via means of a posttranslational lipid modification, the GPI-moiety. Since their discovery in the late 1970s, years of research have provided significant insight into the functions of this ubiquitous modification. In addition to the structure and biosynthesis of the GPI-moiety, perhaps the best-studied feature of this glycolipid is its ability to impart characteristic membrane-trafficking properties to the proteins that it anchors. Study of the mechanism of sorting of GPI-APs has brought to light the importance of lateral heterogeneities in cell membranes, termed rafts, in biological sorting processes. The focus of this review is to examine the emerging role of the GPI-anchor and mechanisms involved in GPI-AP sorting in the context of intracellular trafficking pathways.

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Section: Functions Of the Gpi-anchor: A Surveymentioning

confidence: 99%

Section: Functions Of the Gpi-anchor: A Surveymentioning

confidence: 99%

The GPI-anchor and protein sorting

Chatterjee¹,

Mayor²

2001

CMLS, Cell. Mol. Life Sci.

170

126

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“…GPI anchor intermediates also reach the cell surface via the same pathway [9,13] and, therefore, they are probably exposed to GPI-PLD [19].…”

Section: Introductionmentioning

confidence: 99%

“…GPI-PLD is very abundant in mammalian serum, yet the circulating enzyme does not cleave GPI-anchored proteins on the cell surface. Intracellular GPI-PLD, on the other hand, has been proposed to be responsible for the presence of soluble forms of DAF (decay accelerating factor) as well as other GPIanchored proteins in the circulation and in extracellular fluids [18,19]. Furthermore, in certain pathologies such as cancer in which the enzyme is upregulated [20], tumour-associated GPIanchored proteins (i.e.…”

Section: Introductionmentioning

confidence: 99%

Effect of glycosylphosphatidylinositol (GPI)-phospholipase D overexpression on GPI metabolism

Mann

Hepworth

Raikwar

et al. 2004

Biochemical Journal

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GPI-PLD [glycosylphosphatidylinositol (GPI)-specific phospholipase D (PLD)] is a secreted mammalian enzyme that specifically cleaves GPI-anchored proteins. In addition, the enzyme has been shown to cleave GPI anchor intermediates in cell lysates. The biosynthesis of the GPI anchor is well characterized; however, the mechanisms by which the levels of GPI anchor intermediates are regulated are still unknown. To investigate whether GPI-PLD plays a role in this regulation, we isolated stable HeLa cells overexpressing the enzyme. GPI-PLD-HeLa (GPI-PLD-transfected HeLa) cells showed a 3-fold increase in intracellular GPI-PLD activity and drastically decreased the levels of GPI-anchored proteins when compared with untransfected HeLa controls. Intracellular cleavage of GPIanchored proteins has been suggested to occur early in the secretory pathway and, in agreement with this proposal, GPI-PLD activity in GPI-PLD-HeLa cells was detected not only in the endoplasmic reticulum and Golgi apparatus, but also in the plasma membrane. The enzyme was also active in lipid rafts, membrane microdomains in which GPI-anchored proteins and GPI anchor intermediates are concentrated, indicating that intracellular GPI-PLD cleavage may also occur in this compartment. Pulse-chase paradigms revealed the turnover rate of the last intermediate of the GPI anchor pathway in GPI-PLD-HeLa cells to be accelerated compared with the controls. Furthermore, 1,10-phenanthroline, a GPI-PLD inhibitor, reversed this effect. Our studies demonstrated that GPI-PLD can cleave not only GPIanchored proteins, but also GPI anchor intermediates intracellularly. This observation opens the possibility that GPI-PLD can influence the steady-state levels of GPI-anchored proteins by hydrolysing the anchor before and after its attachment to proteins.

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“…Soluble forms of GPI-anchored proteins have also been found in biological fluids, and serum levels of some of these proteins are increased under certain pathological conditions [3][4][5][6]. Although GPI-specific phospholipase D (GPI-PLD) isolated from serum is not capable of removing GPI-anchored proteins from cell surfaces, cell-associated GPI-PLD is thought to be responsible for releasing GPI-anchored proteins at an intracellular location ( [7][8][9][10] ; for a review, see [11]). Thus the cellular expression level of GPI-PLD could determine the ultimate destination of newly synthesized GPI-anchored proteins : retention on the cell surface or release into the extracellular fluid.…”

Section: Introductionmentioning

confidence: 99%

Tolerance of glycosylphosphatidylinositol (GPI)-specific phospholipase D overexpression by Chinese hamster ovary cell mutants with aberrant GPI biosynthesis

Cai

Stevens

et al. 2002

Biochem. J.

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Mammalian glycosylphosphatidylinositol (GPI)-specific phospholipase D (GPI-PLD) is capable of releasing GPI-anchored proteins by cleavage of the GPI moiety. A previous study indicated that overexpression of GPI-PLD in mouse RAW 264.7 monocytes/macrophages could be cytotoxic, since survivors of stable transfections had enzymic activity no higher than untransfected cells [Du and Low (2001) Infect. Immun. 69, 3214-3223]. We investigated this phenomenon by transfecting bovine GPI-PLD cDNA stably into Chinese hamster ovary (CHO) cells using a bi-cistronic expression system. The surviving transfectants showed an unchanged cellular level of GPI-PLD, supporting the cytotoxicity hypothesis. However, when using a CHO mutant defective in the second step of GPI biosynthesis as host, the expression level of GPI-PLD in stable transfectants was increased by 2.5-fold compared with untransfected or empty-vector-transfected cells. To identify the mechanism, we studied another CHO cell mutant (G9PLAP.D5), which seems to be defective at a later stage in GPI biosynthesis. In sharp contrast with wild-type cells, GPI-PLD activity in G9PLAP.D5 transfected with bovine GPI-PLD cDNA was 100-fold higher than untransfected or empty-vector-transfected cells. This was accompanied by a significant release of alkaline phosphatase into the medium and a decrease in membrane-associated alkaline phosphatase. Taken together, our results indicate that overexpression of GPI-PLD is lethal to wild-type cells, possibly by catalysing the overproduction of GPI-derived toxic substances. We propose that cells with abnormal GPI biosynthesis/processing can escape the toxic effect of these substances.

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Structure and Function of GPI-Specific Phospholipases

Cited by 12 publications

References 113 publications

The GPI-anchor and protein sorting

The GPI-anchor and protein sorting

Effect of glycosylphosphatidylinositol (GPI)-phospholipase D overexpression on GPI metabolism

Tolerance of glycosylphosphatidylinositol (GPI)-specific phospholipase D overexpression by Chinese hamster ovary cell mutants with aberrant GPI biosynthesis

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