SLURP1 Is a Late Marker of Epidermal Differentiation and Is Absent in Mal de Meleda

Favre, Bertrand; Plantard, Laure; Aeschbach, Lorène; Brakch, Noureddine; Christen‐Zaech, Stéphanie; Viragh, Pierre A. de; Sergeant, Ann; Huber, Marcel; Hohl, Daniel

doi:10.1038/sj.jid.5700551

Cited by 85 publications

(108 citation statements)

References 36 publications

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“…Interestingly, two of these mutations, C77R and C99Y, involve the seventh and tenth cysteine, respectively, of the Ly6 domain); another involves the introduction of a proline adjacent to a conserved cysteine (L98P) (16). The latter mutation was intriguing because we have already identified, in a human patient with severe chylomicronemia, a GPIHBP1 mutation involving the introduction of a proline adjacent to a cysteine (15).…”

Section: Volume 284 • Number 44 • October 30 2009mentioning

confidence: 99%

“…Several missense mutations in SLURP1 have been identified in association with Mal de Meleda, the recessive palmoplantar keratoderma (16). Interestingly, two of these mutations, C77R and C99Y, involve the seventh and tenth cysteine, respectively, of the Ly6 domain); another involves the introduction of a proline adjacent to a conserved cysteine (L98P) (16).…”

Section: Volume 284 • Number 44 • October 30 2009mentioning

confidence: 99%

“…That mutation, Q115P, dramatically reduced the ability of GPIHBP1 to bind LPL. Our current findings, along with the Mal de Meleda experience (16), should prompt human geneticists to look for mutations in conserved cysteines in GPI-HBP1 in human patients with chylomicronemia. Indeed, while we were preparing this manuscript, Dallinga-Thie et al (21) reported (at the 2009 Arteriosclerosis, Thrombosis, and Vascular Biology meeting) a C65Y mutation in the Ly6 domain of GPIHBP1 in a young boy with severe chylomicronemia.…”

Section: Volume 284 • Number 44 • October 30 2009mentioning

confidence: 99%

“…Mutation of several (but not all) of the Ly6 cysteines in CD59 reduces the ability of that molecule to inhibit complement-mediated membrane attack (13). Also, missense mutations involving cysteines were found in a secreted Ly6 protein, SLURP1, in association with a recessive palmoplantar keratoderma (16). Unfortunately, the function and the binding partner for SLURP1 are unknown, so no one has been able to use biochemical assays to rigorously assess the impact of cysteine mutations on protein function.…”

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Highly Conserved Cysteines within the Ly6 Domain of GPIHBP1 Are Crucial for the Binding of Lipoprotein Lipase

Beigneux

Gin

Davies

et al. 2009

Journal of Biological Chemistry

138

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GPIHBP1, a glycosylphosphatidylinositol-anchored endothelial cell protein of the lymphocyte antigen 6 (Ly6) family, binds lipoprotein lipase (LPL) avidly and is required for the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 contains two key structural motifs, an acidic domain and an Ly6 motif (a three-fingered domain specified by 10 cysteines). The acidic domain is required for LPL binding, but the importance of the Ly6 domain is less clear. To explore that issue, we transfected cells with a wild-type GPIHBP1 expression vector or mutant GPIHBP1 vectors in which specific cysteines in the Ly6 domain were changed to alanine. The mutant GPIHBP1 proteins reached the cell surface, as judged by antibody binding studies and by the ability of a phosphatidylinositol-specific phospholipase C to release these proteins from the cell surface. However, cells expressing the cysteine mutants could not bind LPL. The acidic domain of the cysteine mutants appeared to remain accessible, as judged by binding studies with an antibody against the acidic domain. We also developed a cell-free assay of LPL binding. We created a rat monoclonal antibody against the carboxyl terminus of mouse GPIHBP1 and used that antibody to coat agarose beads. We then tested the ability of soluble forms of GPIHBP1 that had been immobilized on monoclonal antibodycoated beads to bind LPL. In this assay, wild-type soluble GPI-HBP1 bound LPL avidly, but the cysteine mutants did not. Thus, our studies suggest that a structurally intact Ly6 domain (in addition to the acidic domain) is essential for LPL binding. Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1)2 is an endothelial cell protein that is required for the lipolytic processing of triglyceride-rich lipoproteins in the plasma (1). In the absence of GPI-HBP1, lipolysis of plasma lipoproteins is virtually abolished, leading to severe hypertriglyceridemia (1). Expression of GPI-HBP1 in cultured cells confers the ability to bind lipoprotein lipase (LPL) (1). That finding, along with the fact that GPIHBP1 is located in endothelial cells, led Beigneux et al.(1) to hypothesize that GPIHBP1 serves as an endothelial cell platform for lipolysis.The discovery of the role of GPIHBP1 in lipolysis prompted interest in defining which portions of GPIHBP1 are important for its function (e.g. for its ability to bind LPL). Mature GPI-HBP1 is a relatively short protein with only two noteworthy structural domains (Fig. 1). First, the amino terminus of the protein contains a strongly acidic domain (amino acids 24 -48 in the mouse sequence) with a large number of aspartates and glutamates (2). This negatively charged domain is absolutely critical for binding LPL, a protein that contains two well characterized positively charged "heparin-binding domains" (3-5). Second, GPIHBP1 contains a cysteine-rich Ly6 domain (amino acids 63-135 in the mouse sequence). The function of the Ly6 domain in LPL binding is less clearly defined.The Ly6 domain is an ancient motif containing ...

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Section: Volume 284 • Number 44 • October 30 2009mentioning

confidence: 99%

Section: Volume 284 • Number 44 • October 30 2009mentioning

confidence: 99%

Section: Volume 284 • Number 44 • October 30 2009mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Highly Conserved Cysteines within the Ly6 Domain of GPIHBP1 Are Crucial for the Binding of Lipoprotein Lipase

Beigneux

Gin

Davies

et al. 2009

Journal of Biological Chemistry

138

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“…It has been proposed that lynx1 maintains both a low ACh sensitivity and a safety margin against agonist overstimulation of nAChRs (Miwa et al, 2006). Expression of these endogenous modulators of nAChRs such as lynx1, SLURP-1, or SLURP-2 has not yet been described in the retina, although some works have reported the expression of SLURP1 in whole eye preparation (Mastrangeli et al, 2003) or tears (Favre et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Evidence of alpha 7 nicotinic acetylcholine receptor expression in retinal pigment epithelial cells

et al. 2010

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Some evidence suggests that retinal pigment epithelium (RPE) can express nicotinic acetylcholine receptors (nAChRs) as described for other epithelial cells, where nAChRs have been involved in processes such as cell development, cell death, cell migration, and angiogenesis. This study is designed to determine the expression and activity of a7 nAChRs in RPE cells. Reverse transcriptase (RT)-PCR was performed to test the expression of nicotinic a7 subunit in bovine RPE cells. Protein expression was determined by Western blot and by immunocytochemistry. Expression of nicotinic a7 subunits was also analyzed in cryostat sections of albino rat retina. Changes in protein expression were tested under hypoxic conditions. Functional nAChRs were studied by examining the Ca 2+ transients elicited by nicotine and acetylcholine stimulation in fura-2-loaded cells. Expression of endogenous modulators of nAChRs was analyzed by RT-PCR and Western blot in retina and RPE. Cultured bovine RPE cells expressed nicotinic receptors containing a7 subunit. RT-PCR amplified the expected specific a7 fragment. Western blotting showed expression at the protein level, with a specific band being found at 57 kDa in both cultured and freshly isolated RPE cells. Expression of nAChRs was confirmed for cultured cells by immunofluorescence. Immunohistochemistry confirmed a7 receptor expression in rat RPE retina. a7 receptor expression was down-regulated by long-term hypoxia. A small subpopulation of RPE cultured cells showed functional nAChRs, as evidenced by the selective response elicited by nicotine and acetylcholine stimulation. Expression of the endogenous nicotinic receptors' modulator lynx1 was confirmed in bovine retina and RPE, and expression of lynx1 and other endogenous nicotinic receptor modulators (SLURP1 and RGD1308195) were also confirmed in rat retina. These results suggest that nAChRs could have a significant role in RPE, which may not be related to the traditional role in nerve transmission but could more likely be related to the nonneuronal cholinergic system in the eye.

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“Nagashima-Type” Keratosis as a Novel Entity in the Palmoplantar Keratoderma Category

Kabashima¹,

Sakabe²,

Yamada³

et al. 2008

Arch Dermatol

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Background: "Nagashima-type" keratosis is characterized by transgressive and nonprogressive palmoplantar keratoderma (PPK) with an autosomal recessive trait. Because its clinical manifestations are similar to but milder than those of mal de Meleda, it was originally described as a mild form of Meleda-type PPK. Since then, about 20 cases have been reported in the Japanese-language literature. However, to our knowledge, no cases have been reported from countries other than Japan, presumably because Nagashima-type PPK was not recognized as a distinct entity. It is essential to describe the characteristics of this disease in the English-language literature.Observations: A 17-year-old boy presented with transgressive, hyperhidrotic, erythematous, and hyper-keratotic lesions on his palms and soles that had developed when he was an infant and had progressed until 2 to 3 years earlier. His family history revealed no similar disorders. The symptoms and clinical course were typical for Nagashima-type PPK. A genetic study was performed to search for a mutation in the SLURP1 gene, which is responsible for mal de Meleda, but no mutations were detected in the exon or intron sites of SLURP1. Conclusion:The results of the present genetic study suggest that Nagashima-type keratosis is a novel entity of PPK and is distinct from mal de Meleda.

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SLURP1 Is a Late Marker of Epidermal Differentiation and Is Absent in Mal de Meleda

Cited by 85 publications

References 36 publications

Highly Conserved Cysteines within the Ly6 Domain of GPIHBP1 Are Crucial for the Binding of Lipoprotein Lipase

Highly Conserved Cysteines within the Ly6 Domain of GPIHBP1 Are Crucial for the Binding of Lipoprotein Lipase

Evidence of alpha 7 nicotinic acetylcholine receptor expression in retinal pigment epithelial cells

“Nagashima-Type” Keratosis as a Novel Entity in the Palmoplantar Keratoderma Category

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