|
|
 Previous Article | Table of Contents | Next Article 
The pro region of human neutrophil defensin contains a motif that is
essential for normal subcellular sorting
L Liu and T Ganz
Will Rogers Pulmonary Research Laboratory, University of California, Los
Angeles School of Medicine 90024-1736.
Human defensins (human neutrophil peptides) HNP 1-3 are 29-30 amino acid
antibiotic and cytotoxic peptides highly abundant in the cytoplasmic
granules of polymorphonuclear leukocytes. The peptides are produced from 94
amino acid (aa) prepropeptides by proteolytic cleavage of the signal
sequence and stepwise removal of the 44-45 aa anionic propiece. To study
the role of the propiece, we constructed five in- frame deletions in
preproHNP-1 cDNA between the signal peptidase site and the amino-terminus
of the mature defensin region (aa 21-64). The wild type HNP-1 cDNA and the
deletion mutants were ligated into the pBabe-Neo retroviral vector,
expressed in GP+E86 packaging derivative of NIH 3T3 cells, then transduced
into the 32D cl3 granulocytic cell line. For each construction and both
cell lines, we measured the accumulation of the various defensin forms in
cells and media by 24- hour labeling or pulse-chase with 35S-cysteine- and
immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel
electrophoresis (SDS-PAGE). Deletions in the amino-terminal two-fifths of
the propiece, delta 21-28 and delta 21-38, had only minor effects on
defensin biosynthesis in both cell lines and did not interfere with the
accumulation of mature defensin in the granules of 32D cl3 cells. Deletions
in the carboxyterminal three-fifths of the propiece (delta 21- 51 and delta
21-64) diminished net defensin synthesis, blocked constitutive secretion of
prodefensin in both cell lines, and interfered with defensin accumulation
in cytoplasmic granules of 32D cl3 cells. These effects were reproduced by
the smaller deletion delta 40-51, which contains highly conserved secondary
structure. The propiece segment 40-51 appears to be essential for the
subcellular trafficking and sorting of HNP-1 defensin.
Volume 85,
Issue 4,
pp. 1095-1103,
02/15/1995
Copyright © 1995 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Rajabi, E. de Leeuw, M. Pazgier, J. Li, J. Lubkowski, and W. Lu
The Conserved Salt Bridge in Human {alpha}-Defensin 5 Is Required for Its Precursor Processing and Proteolytic Stability
J. Biol. Chem.,
August 1, 2008;
283(31):
21509 - 21518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Whittington, A. T. Papenfuss, P. Bansal, A. M. Torres, E. S.W. Wong, J. E. Deakin, T. Graves, A. Alsop, K. Schatzkamer, C. Kremitzki, et al.
Defensins and the convergent evolution of platypus and reptile venom genes
Genome Res.,
June 1, 2008;
18(6):
986 - 994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. S. Weeks, H. Tanabe, J. E. Cummings, S. P. Crampton, T. Sheynis, R. Jelinek, T. K. Vanderlick, M. J. Cocco, and A. J. Ouellette
Matrix Metalloproteinase-7 Activation of Mouse Paneth Cell Pro-{alpha}-defensins: SER43{downarrow}ILE44 PROTEOLYSIS ENABLES MEMBRANE-DISRUPTIVE ACTIVITY
J. Biol. Chem.,
September 29, 2006;
281(39):
28932 - 28942.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. Wu, X. Li, E. de Leeuw, B. Ericksen, and W. Lu
Why Is the Arg5-Glu13 Salt Bridge Conserved in Mammalian {alpha}-Defensins?
J. Biol. Chem.,
December 30, 2005;
280(52):
43039 - 43047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Faurschou, S. Kamp, J. B. Cowland, L. Udby, A. H. Johnsen, J. Calafat, H. Winther, and N. Borregaard
Prodefensins are matrix proteins of specific granules in human neutrophils
J. Leukoc. Biol.,
September 1, 2005;
78(3):
785 - 793.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. M. Linden and K. Kaushansky
The Glycan Domain of Thrombopoietin (TPO) Acts in trans to Enhance Secretion of the Hormone and Other Cytokines
J. Biol. Chem.,
September 13, 2002;
277(38):
35240 - 35247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Bülow, U. Gullberg, and I. Olsson
Structural requirements for intracellular processing and sorting of bactericidal/permeability-increasing protein (BPI): comparison with lipopolysaccharide-binding protein
J. Leukoc. Biol.,
November 1, 2000;
68(5):
669 - 678.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. C. Dinauer, J. A. Lekstrom-Himes, and D. C. Dale
Inherited Neutrophil Disorders: Molecular Basis and New Therapies
Hematology,
January 1, 2000;
2000(1):
303 - 318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C L BEVINS, E MARTIN-PORTER, and T GANZ
Defensins and innate host defence of the gastrointestinal tract
Gut,
December 1, 1999;
45(6):
911 - 915.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Andersson, L. Hellman, U. Gullberg, and I. Olsson
The Role of the Propeptide for Processing and Sorting of Human Myeloperoxidase
J. Biol. Chem.,
February 20, 1998;
273(8):
4747 - 4753.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Sorensen, K. Arnljots, J. B. Cowland, D. F. Bainton, and N. Borregaard
The Human Antibacterial Cathelicidin, hCAP-18, Is Synthesized in Myelocytes and Metamyelocytes and Localized to Specific Granules in Neutrophils
Blood,
October 1, 1997;
90(7):
2796 - 2803.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Borregaard and J. B. Cowland
Granules of the Human Neutrophilic Polymorphonuclear Leukocyte
Blood,
May 15, 1997;
89(10):
3503 - 3521.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Garwicz, A. Lindmark, and U. Gullberg
Human Cathepsin G Lacking Functional Glycosylation Site Is Proteolytically Processed and Targeted for Storage in Granules after Transfection to the Rat Basophilic/Mast Cell Line RBL or the Murine Myeloid Cell Line 32D
J. Biol. Chem.,
November 24, 1995;
270(47):
28413 - 28418.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
