The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma

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Standard

The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma. / Christoffersen, Christina; Ahnström, Josefin; Axler, Olof; Christensen, Erik Ilsø; Dahlbäck, Björn; Nielsen, Lars Bo.

I: Journal of Biological Chemistry, Bind 283, Nr. 27, 2008, s. 18765-72.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Christoffersen, C, Ahnström, J, Axler, O, Christensen, EI, Dahlbäck, B & Nielsen, LB 2008, 'The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma', Journal of Biological Chemistry, bind 283, nr. 27, s. 18765-72. https://doi.org/10.1074/jbc.M800695200

APA

Christoffersen, C., Ahnström, J., Axler, O., Christensen, E. I., Dahlbäck, B., & Nielsen, L. B. (2008). The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma. Journal of Biological Chemistry, 283(27), 18765-72. https://doi.org/10.1074/jbc.M800695200

Vancouver

Christoffersen C, Ahnström J, Axler O, Christensen EI, Dahlbäck B, Nielsen LB. The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma. Journal of Biological Chemistry. 2008;283(27):18765-72. https://doi.org/10.1074/jbc.M800695200

Author

Christoffersen, Christina ; Ahnström, Josefin ; Axler, Olof ; Christensen, Erik Ilsø ; Dahlbäck, Björn ; Nielsen, Lars Bo. / The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma. I: Journal of Biological Chemistry. 2008 ; Bind 283, Nr. 27. s. 18765-72.

Bibtex

@article{38c004f0acd611ddb538000ea68e967b,
title = "The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma",
abstract = "Lipoproteins consist of lipids solubilized by apolipoproteins. The lipid-binding structural motifs of apolipoproteins include amphipathic alpha-helixes and beta-sheets. Plasma apolipoprotein (apo) M lacks an external amphipathic motif but, nevertheless, is exclusively associated with lipoproteins (mainly high density lipoprotein). Uniquely, however, apoM is secreted to plasma without cleavage of its hydrophobic NH(2)-terminal signal peptide. To test whether the signal peptide serves as a lipoprotein anchor for apoM in plasma, we generated mice expressing a mutated apoM(Q22A) cDNA in the liver (apoM(Q22A)-Tg mice (transgenic mice)) and compared them with mice expressing wild-type human apoM (apoM-Tg mice). The substitution of the amino acid glutamine 22 with alanine in apoM(Q22A) results in secretion of human apoM without a signal peptide. The human apoM mRNA level in liver and the amount of human apoM protein secretion from hepatocytes were similar in apoM-Tg and apoM(Q22A)-Tg mice. Nevertheless, human apoM was not detectable in plasma of apoM(Q22A)-Tg mice, whereas it was easily measured in the apoM-Tg mice. To examine the plasma metabolism, recombinant apoM lacking the signal peptide was produced in Escherichia coli and injected into wild-type mice. The apoM without signal peptide did not associate with lipoproteins and was rapidly cleared in the kidney. Accordingly, ligation of the kidney arteries in apoM(Q22A)-Tg mice resulted in rapid accumulation of human apoM in plasma. The data suggest that hydrophobic signal peptide sequences, if preserved upon secretion, can anchor plasma proteins in lipoproteins. In the case of apoM, this mechanism prevents rapid loss by filtration in the kidney.",
author = "Christina Christoffersen and Josefin Ahnstr{\"o}m and Olof Axler and Christensen, {Erik Ils{\o}} and Bj{\"o}rn Dahlb{\"a}ck and Nielsen, {Lars Bo}",
note = "Keywords: Amino Acid Motifs; Amino Acid Substitution; Animals; Apolipoproteins; Hepatocytes; Humans; Hydrophobicity; Kidney; Lipoproteins, HDL; Liver; Mice; Mice, Transgenic; Protein Sorting Signals",
year = "2008",
doi = "10.1074/jbc.M800695200",
language = "English",
volume = "283",
pages = "18765--72",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "27",

}

RIS

TY - JOUR

T1 - The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma

AU - Christoffersen, Christina

AU - Ahnström, Josefin

AU - Axler, Olof

AU - Christensen, Erik Ilsø

AU - Dahlbäck, Björn

AU - Nielsen, Lars Bo

N1 - Keywords: Amino Acid Motifs; Amino Acid Substitution; Animals; Apolipoproteins; Hepatocytes; Humans; Hydrophobicity; Kidney; Lipoproteins, HDL; Liver; Mice; Mice, Transgenic; Protein Sorting Signals

PY - 2008

Y1 - 2008

N2 - Lipoproteins consist of lipids solubilized by apolipoproteins. The lipid-binding structural motifs of apolipoproteins include amphipathic alpha-helixes and beta-sheets. Plasma apolipoprotein (apo) M lacks an external amphipathic motif but, nevertheless, is exclusively associated with lipoproteins (mainly high density lipoprotein). Uniquely, however, apoM is secreted to plasma without cleavage of its hydrophobic NH(2)-terminal signal peptide. To test whether the signal peptide serves as a lipoprotein anchor for apoM in plasma, we generated mice expressing a mutated apoM(Q22A) cDNA in the liver (apoM(Q22A)-Tg mice (transgenic mice)) and compared them with mice expressing wild-type human apoM (apoM-Tg mice). The substitution of the amino acid glutamine 22 with alanine in apoM(Q22A) results in secretion of human apoM without a signal peptide. The human apoM mRNA level in liver and the amount of human apoM protein secretion from hepatocytes were similar in apoM-Tg and apoM(Q22A)-Tg mice. Nevertheless, human apoM was not detectable in plasma of apoM(Q22A)-Tg mice, whereas it was easily measured in the apoM-Tg mice. To examine the plasma metabolism, recombinant apoM lacking the signal peptide was produced in Escherichia coli and injected into wild-type mice. The apoM without signal peptide did not associate with lipoproteins and was rapidly cleared in the kidney. Accordingly, ligation of the kidney arteries in apoM(Q22A)-Tg mice resulted in rapid accumulation of human apoM in plasma. The data suggest that hydrophobic signal peptide sequences, if preserved upon secretion, can anchor plasma proteins in lipoproteins. In the case of apoM, this mechanism prevents rapid loss by filtration in the kidney.

AB - Lipoproteins consist of lipids solubilized by apolipoproteins. The lipid-binding structural motifs of apolipoproteins include amphipathic alpha-helixes and beta-sheets. Plasma apolipoprotein (apo) M lacks an external amphipathic motif but, nevertheless, is exclusively associated with lipoproteins (mainly high density lipoprotein). Uniquely, however, apoM is secreted to plasma without cleavage of its hydrophobic NH(2)-terminal signal peptide. To test whether the signal peptide serves as a lipoprotein anchor for apoM in plasma, we generated mice expressing a mutated apoM(Q22A) cDNA in the liver (apoM(Q22A)-Tg mice (transgenic mice)) and compared them with mice expressing wild-type human apoM (apoM-Tg mice). The substitution of the amino acid glutamine 22 with alanine in apoM(Q22A) results in secretion of human apoM without a signal peptide. The human apoM mRNA level in liver and the amount of human apoM protein secretion from hepatocytes were similar in apoM-Tg and apoM(Q22A)-Tg mice. Nevertheless, human apoM was not detectable in plasma of apoM(Q22A)-Tg mice, whereas it was easily measured in the apoM-Tg mice. To examine the plasma metabolism, recombinant apoM lacking the signal peptide was produced in Escherichia coli and injected into wild-type mice. The apoM without signal peptide did not associate with lipoproteins and was rapidly cleared in the kidney. Accordingly, ligation of the kidney arteries in apoM(Q22A)-Tg mice resulted in rapid accumulation of human apoM in plasma. The data suggest that hydrophobic signal peptide sequences, if preserved upon secretion, can anchor plasma proteins in lipoproteins. In the case of apoM, this mechanism prevents rapid loss by filtration in the kidney.

U2 - 10.1074/jbc.M800695200

DO - 10.1074/jbc.M800695200

M3 - Journal article

C2 - 18460466

VL - 283

SP - 18765

EP - 18772

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 27

ER -

ID: 8466157