Stimulation of Cellular Sphingomyelin Import by the Chemokine Connective Tissue-activating Peptide III

Stoeckelhuber, Mechthild; Dobner, Petra; Baumgärtner, Petra; Ehlert, Jan E.; Brandt, Ernst; Mentele, Reinhard; Adam, Dieter; Engelmann, Bernd

doi:10.1074/jbc.m003709200

Cited by 8 publications

(5 citation statements)

References 47 publications

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“…PCI is shown to selectively extract PE from lipid particles, consecutively inserting the lipid into the plasma membrane of various cells. PCI thus belongs to a new class of proteins promoting the cellular uptake of selective lipids, including those specifi c for phosphatidylinositol (Wang and Munford, 1999) and sphingoymyelin (Stoeckelhuber et al, 2000). The latter proteins do not share structural homologies with PCI, a situation known from the intracellular lipid transfer proteins (Wirtz, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…For the determination of the intervesicular phospholipid exchange, pylabeled donor vesicles and unlabeled acceptor vesicles were coincubated for different time periods, the suspensions were passed over an anion exchange column (Bio-Rad Laboratories), and the fl uorescence was determined in Triton X-100 (Sigma-Aldrich) solubilisates of the acceptor vesicles as described previously (Stoeckelhuber et al, 2000). The vesicle preparations and incubations were performed in the presence of 10 nM butylated hydroxytoluene and under argon or nitrogen.…”

Section: Phospholipid Exchangementioning

confidence: 99%

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Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor

Baumgärtner¹,

Geiger²,

Zieseniss³

et al. 2007

The Journal of Cell Biology

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Although their contribution remains unclear, lipids may facilitate noncanonical routes of protein internalization into cells such as those used by cell-penetrating proteins. We show that protein C inhibitor (PCI), a serine protease inhibitor (serpin), rapidly transverses the plasma membrane, which persists at low temperatures and enables its nuclear targeting in vitro and in vivo. Cell membrane translocation of PCI necessarily requires phosphatidylethanolamine (PE). In parallel, PCI acts as a lipid transferase for PE. The internalized serpin promotes phagocytosis of bacteria, thus suggesting a function in host defense. Membrane insertion of PCI depends on the conical shape of PE and is associated with the formation of restricted aqueous compartments within the membrane. Gain- and loss-of-function mutations indicate that the transmembrane passage of PCI requires a branched cavity between its helices H and D, which, according to docking studies, precisely accommodates PE. Our findings show that its specific shape enables cell surface PE to drive plasma membrane translocation of cell-penetrating PCI.

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Section: Discussionmentioning

confidence: 99%

Section: Phospholipid Exchangementioning

confidence: 99%

Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor

Baumgärtner¹,

Geiger²,

Zieseniss³

et al. 2007

The Journal of Cell Biology

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“…18,33 NAP-2 is also a potent chemotactic agent for neutrophils. 34 Other functions of importance have been attributed to various CXCL7 peptides: CTAP-III may be responsible for intracellular transport of sphingomyelin, 35 ␤-TG may be chemotactic to fibroblasts. 36 Other less defined functions like heparinase activity of PBP and CTAP-III may be important for the modification of the matrix proteins.…”

Section: Discussionmentioning

confidence: 99%

Monocyte-derived CXCL7 peptides in the marrow microenvironment

Pillai

Iwata

Awaya

et al. 2006

Blood

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The marrow microenvironment consists of several different interacting cell types, including hematopoietic-derived monocyte/macrophages and nonhematopoieticderived stromal cells. Gene-expression profiles of stromal cells and monocytes cultured together differ from those of each population alone. Here, we report that CXCL7 gene expression, previously described as limited to the megakaryocyte lineage, is expressed by monocytes cocultured with stromal cells. CXCL7 gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and secretion of protein was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot. At least 2 stromal-derived activities, one yet to be identified, were required for optimal expression of CXCL7 by monocytes. NAP-2, the shortest form of CXCL7 detected in the coculture media, was confirmed to decrease the size and number of CFU-Meg colonies. The propeptide LDGF, previously reported to be mitogenic for fibroblasts, was not secreted by stimulated monocytes. The recombinant form of LDGF produced in a prokaryotic expression system did not have biologic activity in our hands. The monocytic source of CXCL7 was also detected by immunohistochemistry in normal bone marrow biopsies, indicating an in vivo function. We conclude that stromal-stimulated monocytes can serve as an additional source for CXCL7 peptides in the microenvironment and may contribute to the local regulation of megakaryocytopoiesis. ( IntroductionHematopoietic regulation takes place within the marrow microenvironment (ME), which is defined by function as a complex of cells and cell products critical for the maintenance and regulation of stem cells and their progeny. The ME contains mesenchymal cells (eg, fibroblasts, adipocytes, and smooth muscle, all referred to as stromal cells); it also contains hematopoietic-derived monocytes/ macrophages. Primary long-term cultures (LTCs) of marrow stroma have been used to approximate the ME in vitro. 1 The model has proven useful for identifying cells and factors that play a role in supporting hematopoiesis. However, the heterogeneity of the cell types that comprise a functional LTC have led many investigators to generate stromal cell lines to dissect ME functional components. [2][3][4] We have previously reported on immortalized stromal lines generated by transducing human stromal cells with E6/E7 genes from human papilloma virus (HPV). 5,6 Two of these lines have been studied and characterized in detail. One, designated HS27a, supports maintenance of early hematopoietic progenitors in "cobblestone areas" and does not secrete growth factors. The other, designated HS5, does not support cobblestone areas but does secrete copious amounts of growth factors. These lines have hence been hypothesized to represent cell types that contribute to functionally distinct niches.Monocyte-derived macrophages have long been known as critical components of both the in vivo and in vitro ME. In vivo, the macrophage can function as the "nurse cell" of the ery...

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“…(484) Hydrolytic enzymes for sphingolipids are also found in other locations in the cell to produce bioactive products for cell signaling 5,6 and rearrangement of membrane architecture. 23,485 The complete balance sheet for sphingolipids additionally includes uptake of sphingolipids from exogenous sources (such as albumin and lipoproteins) 486,487 and losses by efflux,(488) lipoprotein secretion, 354,489 and shedding of membrane vesicles containing sphingolipids. (490)…”

Section: Sphingolipid Metabolic Pathwaysmentioning

confidence: 99%

“…This usually occurs via lysosomal enzymes and, if the intermediates are not recycled, is followed by the irreversible degradation of the sphingoid base to products that are no longer categorized as sphingolipids (e.g., a fatty aldehyde and ethanolamine phosphate) in the cytosol . Hydrolytic enzymes for sphingolipids are also found in other locations in the cell to produce bioactive products for cell signaling , and rearrangement of membrane architecture. , The complete balance sheet for sphingolipids additionally includes uptake of sphingolipids from exogenous sources (such as albumin and lipoproteins) , and losses by efflux, lipoprotein secretion, , and shedding of membrane vesicles containing sphingolipids …”

Section: Sphingolipid Metabolic Pathwaysmentioning

confidence: 99%

Sphingolipid and Glycosphingolipid Metabolic Pathways in the Era of Sphingolipidomics

2011

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Stimulation of Cellular Sphingomyelin Import by the Chemokine Connective Tissue-activating Peptide III

Cited by 8 publications

References 47 publications

Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor

Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor

Monocyte-derived CXCL7 peptides in the marrow microenvironment

Sphingolipid and Glycosphingolipid Metabolic Pathways in the Era of Sphingolipidomics

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