Calcium binding studies of peptides of human phospholipid scramblases 1 to 4 suggest that scramblases are new class of calcium binding proteins in the cell

Sahu, Santosh Kumar; Aradhyam, Gopala Krishna; Gummadi, Sathyanarayana N.

doi:10.1016/j.bbagen.2009.06.008

Cited by 24 publications

(29 citation statements)

References 48 publications

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“…Similar mutation of Asp 275 in the predicted Ca 2 + -binding motif of hPLSCR1 has been shown to decrease the scramblase acti vity by ∼ 90 % compared with wild type (Stout et al , 1998 ). The affi nity of Ca 2 + for hPLSCR4 was found to be the highest and is consistent with earlier reported data on metal ion binding to EF-hand peptide of hPLSCR4 (Sahu et al , 2009 ). The decreased binding affi nity of Ca 2 + for Asp 290 → Ala mutant indicates the importance of this residue for Ca 2 + binding and also the decreased rate of PL scrambling by Asp 290 → Ala mutant confi rms that PL-mobilizing activity of hPLSCR4 is metal ion dependent.…”

Section: Discussionsupporting

confidence: 90%

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Biochemical and functional characterization of human phospholipid scramblase 4 (hPLSCR4)

Francis

Gummadi

2012

Biological Chemistry

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Human phospholipid scramblase 4 (hPLSCR4), an isoform of the scramblase family, is a type II single-pass transmembrane protein whose function remains unknown. To understand its role, recombinant hPLSCR4 was obtained by cloning the ORF into a pET28 a(+) vector and overexpressed in Escherichia coli. Functional assay showed that Ca2+, Mg2+, and Zn2+ activate hPLSCR4 and mediate scrambling activity independent of the phospholipid head group. Far-UV-CD and fluorescence spectroscopy revealed that Ca2+ and Mg2+ binding induces conformation change in hPLSCR4, exposing hydrophobic patches of the protein, and Ca2+ has more affinity than Mg2+ and Zn2+. Stains-all studies further confirm that hPLSCR4 is a Ca2+-binding protein. Point mutation (Asp290→Ala) in hPLSCR4 decreased the Ca2+-binding affinity as well as Tb3+ luminescence, suggesting residues of the predicted Ca2+-binding motif are involved in Ca2+ binding. Functional reconstitution with (Asp290→Ala) mutant led to ~50% and ~40% decrease in scramblase activity in the presence of Ca2+ and Mg2+, respectively.

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Section: Discussionsupporting

confidence: 90%

“…Similar differences in hPLSCR1 (overexpressed and purifi ed from E. coli ) activity were observed for Ca 2 + vs. other metal ions, where Zn 2 + showed more activity than calcium (Stout et al , 1998 ). Additionally, for the EF-hand peptide of hPLSCR4, the Mg 2 + -binding affi nity was higher than Ca 2 + binding (Sahu et al , 2009 ).…”

Section: Discussionsupporting

confidence: 74%

Biochemical and functional characterization of human phospholipid scramblase 4 (hPLSCR4)

Francis

Gummadi

2012

Biological Chemistry

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“…ATP10A , one of the putative aminophospholipid translocases, and bidirectional phospholipid translocator scramblase 1 were expressed at higher levels in the hBMSCs of the old donors. Furthermore, the gene expression of scramblase 4 was increased during expansion ( 67,68 ) Thus our data indicate physiologically important GPL remodeling with functional consequences in the hBMSCs.…”

Section: Immunosuppressive Capacity Of Hbmscs Decreases During Cell Ementioning

confidence: 75%

Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality

Kilpinen

Tigistu-Sahle

Oja

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org Supplementary key words glycerophospholipid profi le • mesenchymal stem cell • arachidonic acid • docosahexaenoic acid • lipid signaling • mass spectrometry Human mesenchymal stem/stromal cells (hMSC) are currently being studied in a number of clinical applications, for example, to improve the engraftment of hematopoietic stem cell transplant, to promote myocardial repair, and to control immunological responses in graft versus host diseases, autoimmune diseases, and solid organ transplantations ( 1-5 ). In addition to being immunologically privileged, these cells can modulate both innate and adaptive immune responses in vitro and in vivo. hMSCs have been shown to be able to inhibit T-cell proliferation, inhibit dendritic cell maturation ( 6 ), recruit regulatory T-cells ( 7,8 ), and modulate B-cell functions ( 9 ). The mechanisms by which these cells exert their immune modulatory functions are still unclear, but it is likely that both direct cell-cell contacts and the secretion of soluble factors are needed. Several cytokines, growth factors, enzymes, and lipid mediators, such as transforming growth factor ␤ 1, the

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“…Recent work confirms the importance of the C-terminal alpha helix for both calcium binding and scrambling activity [121, 139]. It is hypothesized that calcium binding is followed by a conformational change and perhaps self-aggregation [131, 137, 138]. In the absence of calcium, acidic conditions (pH < 6.0) activate PLSCR1 in erythrocyte-derived inside out vesicles [130].…”

Section: The Response Of Phospholipid Scramblase 1 To Hypoxiamentioning

confidence: 90%

“…Activation of PLSCR1 involves the binding of calcium or potentially other divalent cations [128, 137] to a predicted single cation binding site [137] in the cytoplasmic portion. Several studies have demonstrated an increase in phospholipid scrambling in the presence of calcium [128, 129, 138].…”

Section: The Response Of Phospholipid Scramblase 1 To Hypoxiamentioning

confidence: 99%

Membrane lipid interactions in intestinal ischemia/reperfusion-induced Injury

Slone

Fleming

2014

Clinical Immunology

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Ischemia, lack of blood flow, and reperfusion, return of blood flow, is a common phenomenon affecting millions of Americans each year. Roughly 30,000 Americans per year experience intestinal ischemia-reperfusion (IR), which is associated with a high mortality rate. Previous studies of the intestine established a role for neutrophils, eicosanoids, the complement system and naturally occurring antibodies in IR-induced pathology. Furthermore, data indicate involvement of a lipid or lipid-like moiety in mediating IR-induced damage. It has been proposed that exposure of neo-antigens are recognized by antibodies, triggering action of the complement cascade. While it is evident that the pathophysiology of IR-induced injury is complex and multi-factorial, we focus this review on the involvement of eicosanoids, phospholipids and neo-antigens in the early pathogenesis. Lipid changes occurring in response to IR, neo-antigens exposed and the role of a phospholipid transporter, phospholipid scramblase 1 will be discussed.

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Calcium binding studies of peptides of human phospholipid scramblases 1 to 4 suggest that scramblases are new class of calcium binding proteins in the cell

Cited by 24 publications

References 48 publications

Biochemical and functional characterization of human phospholipid scramblase 4 (hPLSCR4)

Biochemical and functional characterization of human phospholipid scramblase 4 (hPLSCR4)

Aging bone marrow mesenchymal stromal cells have altered membrane glycerophospholipid composition and functionality

Membrane lipid interactions in intestinal ischemia/reperfusion-induced Injury

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