Home LiteratureArticle Details
PMID: 8670795 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Neuroserpin, an axonally secreted serine protease inhibitor.

The EMBO journal ·Vol. 15 ·No. 12 ·1996-06-17 ·Pages 2944-53

Osterwalder T, Contartese J, Stoeckli ET, Kuhn TB, Sonderegger P

Abstract

We have identified and chromatographically purified an axonally secreted glycoprotein of CNS and PNS neurons. Several peptides derived from it were microsequenced. Based on these sequences, a fragment of the corresponding cDNA was amplified and used as a probe to isolate a full length cDNA from a chicken brain cDNA library. Because the deduced amino acid sequence qualified the protein as a novel member of the serpin family of serine protease inhibitors, we called it neuroserpin. Analysis of the primary structural features further characterized neuroserpin as a heparin-independent, functional inhibitor of a trypsin-like serine protease. In situ hybridization revealed a predominantly neuronal expression during the late stages of neurogenesis and in the adult brain in regions which exhibit synaptic plasticity. Thus, neuroserpin might function as an axonally secreted regulator of the local extracellular proteolysis involved in the reorganization of the synaptic connectivity during development and synapse plasticity in the adult.

MeSH Terms
Amino Acid Sequence Animals Axons/metabolism Base Sequence Cells, Cultured Chickens Chromatography, Liquid Cloning, Molecular DNA, Complementary Electrophoresis, Polyacrylamide Gel Ganglia, Spinal/metabolism Molecular Sequence Data Motor Neurons/metabolism Neuropeptides/genetics,isolation & purification,metabolism RNA, Messenger/genetics,metabolism Sequence Homology, Amino Acid Serine Proteinase Inhibitors/genetics,isolation & purification,metabolism Serpins/genetics,isolation & purification,metabolism Spinal Cord/cytology,metabolism
Chemicals
DNA, Complementary Neuropeptides RNA, Messenger Serine Proteinase Inhibitors Serpins neuroserpin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Osterwalder T
Institute of Biochemistry, University of Zurich, Switzerland.
Contartese J
Stoeckli E T
Kuhn T B
Sonderegger P
References (62)
62 references, click to expand
  1. Plasminogen activator secretion by granule neurons in cultures of developing cerebellum.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7810-4 PMID: 6950420
  2. Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation.
    Nature. 1993 Feb 4;361(6411):453-7 PMID: 8429885
  3. Axonal proteins of presynaptic neurons during synaptogenesis.
    Science. 1983 Sep 23;221(4617):1294-7 PMID: 6612344
  4. The heparin-binding site of antithrombin III. Identification of a critical tryptophan in the amino acid sequence.
    J Biol Chem. 1984 Jan 25;259(2):939-41 PMID: 6693405
  5. A few axonal proteins distinguish ventral spinal cord neurons from dorsal root ganglion neurons.
    J Cell Biol. 1984 Jan;98(1):364-8 PMID: 6707097
  6. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids.
    Anal Biochem. 1984 Apr;138(1):141-3 PMID: 6731838
  7. On the size of the active site in proteases. I. Papain.
    Biochem Biophys Res Commun. 1967 Apr 20;27(2):157-62 PMID: 6035483
  8. A general method applicable to the search for similarities in the amino acid sequence of two proteins.
    J Mol Biol. 1970 Mar;48(3):443-53 PMID: 5420325
  9. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  10. The development of the chick optic tectum. II. Autoradiographic studies.
    Brain Res. 1971 May 21;28(3):421-41 PMID: 5111721
  11. High resolution two-dimensional electrophoresis of proteins.
    J Biol Chem. 1975 May 25;250(10):4007-21 PMID: 236308
  12. Local control of neurite development by nerve growth factor.
    Proc Natl Acad Sci U S A. 1977 Oct;74(10):4516-9 PMID: 270699
  13. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  14. Independent control of the local environment of somas and neurites.
    Methods Enzymol. 1979;58:302-7 PMID: 423772
  15. A highly sensitive silver stain for detecting proteins and peptides in polyacrylamide gels.
    Anal Biochem. 1979 Sep 15;98(1):231-7 PMID: 94518
  16. Protease-nexin: a cellular component that links thrombin and plasminogen activator and mediates their binding to cells.
    Cell. 1980 Aug;21(1):37-45 PMID: 6157479
  17. A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels.
    Anal Biochem. 1980 Jul 1;105(2):361-3 PMID: 6161559
  18. Environmentally regulated expression of soluble extracellular proteins of sympathetic neurons.
    J Biol Chem. 1981 Apr 25;256(8):4063-70 PMID: 7217069
  19. Plasminogen activator release at the neuronal growth cone.
    Science. 1981 Sep 25;213(4515):1532-4 PMID: 7197054
  20. Differential modulation of the expression of axonal proteins by non-neuronal cells of the peripheral and central nervous system.
    EMBO J. 1985 Jun;4(6):1395-401 PMID: 4029116
  21. A glia-derived neurite-promoting factor with protease inhibitory activity.
    EMBO J. 1985 Aug;4(8):1963-6 PMID: 4065100
  22. A glia-derived neurite promoting factor with protease inhibitory activity belongs to the protease nexins.
    Cell. 1986 Dec 5;47(5):687-93 PMID: 2877744
  23. Isolation of full-length putative rat lysophospholipase cDNA using improved methods for mRNA isolation and cDNA cloning.
    Biochemistry. 1987 Mar 24;26(6):1617-25 PMID: 3593682
  24. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  25. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs.
    Nucleic Acids Res. 1987 Oct 26;15(20):8125-48 PMID: 3313277
  26. Formation of topographic maps.
    Annu Rev Neurosci. 1988;11:289-327 PMID: 3284443
  27. Enzymatic amplification of specific cDNA inserts from lambda gt11 libraries.
    Nucleic Acids Res. 1988 Sep 12;16(17):8718 PMID: 2843825
  28. Decrease in plasminogen activator correlates with synapse elimination during neonatal development of mouse skeletal muscle.
    Proc Natl Acad Sci U S A. 1989 Jan;86(1):362-6 PMID: 2492103
  29. Onset and development of intersegmental projections in the chick embryo spinal cord.
    J Comp Neurol. 1988 Sep 8;275(2):159-80 PMID: 2464626
  30. Absence of large-scale conformational change upon limited proteolysis of ovalbumin, the prototypic serpin.
    J Biol Chem. 1989 Mar 5;264(7):3781-5 PMID: 2645277
  31. Identification of proteins secreted from axons of embryonic dorsal-root-ganglia neurons.
    Eur J Biochem. 1989 Mar 15;180(2):249-58 PMID: 2924765
  32. Purification of axonin-1, a protein that is secreted from axons during neurogenesis.
    EMBO J. 1989 Jan;8(1):55-63 PMID: 2714258
  33. Induction of glia-derived nexin after lesion of a peripheral nerve.
    Nature. 1989 Nov 30;342(6249):548-50 PMID: 2685611
  34. Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed glycosaminoglycan-binding site of heparin cofactor II.
    J Biol Chem. 1990 Jan 5;265(1):286-91 PMID: 2104620
  35. Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins.
    Biochemistry. 1989 Nov 14;28(23):8951-66 PMID: 2690952
  36. Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways.
    Annu Rev Neurosci. 1990;13:129-54 PMID: 2183671
  37. Functional sites of glia-derived nexin (GDN): importance of the site reacting with the protease.
    Biochemistry. 1990 Mar 6;29(9):2417-21 PMID: 2337608
  38. The expression of tissue and urokinase-type plasminogen activators in neural development suggests different modes of proteolytic involvement in neuronal growth.
    Development. 1992 Nov;116(3):625-37 PMID: 1289056
  39. Plasminogen activator inhibitor 1, the primary regulator of fibrinolysis, in normal human cerebrospinal fluid.
    J Neurosci Res. 1993 Feb 15;34(3):340-5 PMID: 8455210
  40. Effects of mutations in the hinge region of serpins.
    Biochemistry. 1993 Aug 3;32(30):7650-7 PMID: 8347575
  41. The role of conformational change in serpin structure and function.
    Bioessays. 1993 Jul;15(7):461-7 PMID: 8379949
  42. Urokinase-type plasminogen activator expression by neurons and oligodendrocytes during process outgrowth in developing rat brain.
    Eur J Neurosci. 1993 Jun 1;5(6):633-47 PMID: 8261137
  43. Overexpression of urokinase-type plasminogen activator in transgenic mice is correlated with impaired learning.
    Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3196-200 PMID: 8159723
  44. A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes.
    Histochemistry. 1993 Dec;100(6):431-40 PMID: 7512949
  45. Structural aspects of serpin inhibition.
    FEBS Lett. 1994 May 16;344(2-3):117-24 PMID: 8187869
  46. Localization of the heparin-binding site of glia-derived nexin/protease nexin-1 by site-directed mutagenesis.
    Biochemistry. 1994 Jun 21;33(24):7731-5 PMID: 8011637
  47. Proteolytic action of thrombin is required for electrical activity-dependent synapse reduction.
    Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10300-4 PMID: 7524091
  48. Neuromuscular contacts of expanded motor units in rat soleus muscles are rescued by leupeptin.
    Neuroscience. 1994 Nov;63(1):327-38 PMID: 7898657
  49. Axonin-1, Nr-CAM, and Ng-CAM play different roles in the in vivo guidance of chick commissural neurons.
    Neuron. 1995 Jun;14(6):1165-79 PMID: 7541632
  50. A serine proteinase involved in contact mediated repulsion of retinal growth cones by DRG neurites.
    J Neurosci. 1995 Oct;15(10):6605-18 PMID: 7472422
  51. Crystal structure of plakalbumin, a proteolytically nicked form of ovalbumin. Its relationship to the structure of cleaved alpha-1-proteinase inhibitor.
    J Mol Biol. 1990 Jun 5;213(3):513-28 PMID: 2352279
  52. Separation of peptides dissolved in a sodium dodecyl sulfate solution by reversed-phase liquid chromatography: removal of sodium dodecyl sulfate from peptides using an ion-exchange precolumn.
    Anal Biochem. 1990 May 1;186(2):264-8 PMID: 2363498
  53. Crystal structure of ovalbumin as a model for the reactive centre of serpins.
    Nature. 1990 Sep 6;347(6288):99-102 PMID: 2395463
  54. Point mutations in AAUAAA and the poly (A) addition site: effects on the accuracy and efficiency of cleavage and polyadenylation in vitro.
    Nucleic Acids Res. 1990 Oct 11;18(19):5799-805 PMID: 2170946
  55. Structure-function studies of the SERPIN plasminogen activator inhibitor type 1. Analysis of chimeric strained loop mutants.
    J Biol Chem. 1990 Nov 25;265(33):20293-301 PMID: 1700786
  56. Characterization of the serpin, alpha 1-antichymotrypsin, in normal human cerebrospinal fluid.
    J Neurochem. 1992 Jan;58(1):88-94 PMID: 1727448
  57. Production of thrombin and antithrombin III by brain and astroglial cell cultures.
    Brain Res Mol Brain Res. 1991 Oct;11(3-4):355-8 PMID: 1661827
  58. The axonally secreted cell adhesion molecule, axonin-1. Primary structure, immunoglobulin-like and fibronectin-type-III-like domains and glycosyl-phosphatidylinositol anchorage.
    Eur J Biochem. 1992 Mar 1;204(2):453-63 PMID: 1311675
  59. Saturation mutagenesis of the plasminogen activator inhibitor-1 reactive center.
    J Biol Chem. 1992 Apr 15;267(11):7588-95 PMID: 1559996
  60. Developmental mechanisms that generate precise patterns of neuronal connectivity.
    Cell. 1993 Jan;72 Suppl:77-98 PMID: 8428376
  61. Development of the visual system of the chick--a review.
    J Hirnforsch. 1992;33(6):673-702 PMID: 1494045
  62. Patterns of amino acids near signal-sequence cleavage sites.
    Eur J Biochem. 1983 Jun 1;133(1):17-21 PMID: 6852022
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-06-17
Pages
2944-53
Language
English
Region
England
NLM ID
8208664
PMCID
PMC450235
Subset
IM
Databases
GENBANK
Z71930
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com