Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin.

Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Research Abstract Details 

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Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Abstract Text:

Shoji Ishigami,Maria Sandkvist,Foon Tsui,Elizabeth Moore,Timothy A Coleman,Daniel A Lawrence,

Ns (neuroserpin) is a member of the serpin (serine protease inhibitor) gene family that is primarily expressed within the central nervous system. Its principal target protease is tPA (tissue plasminogen activator), which is thought to contribute to synaptic plasticity and to be secreted in a stimulus-dependent manner. In the present study, we demonstrate in primary neuronal cultures that Ns co-localizes in LDCVs (large dense core vesicles) with the regulated secretory protein chromogranin B. We also show that Ns secretion is regulated and can be specifically induced 4-fold by secretagogue treatment. A novel 13-amino-acid sorting signal located at the C-terminus of Ns is identified that is both necessary and sufficient to target Ns to the regulated secretion pathway. Its deletion renders Ns no longer responsive to secretagogue stimulation, whereas PAI-Ns [Ns (neuroserpin)-PAI-1 (plasminogen activator inhibitor-1) chimaera appending the last 13 residues of Ns sequence to the C-terminus of PAI-1] shifts PAI-1 secretion into a regulated secretory pathway.

Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Publishing Authors By Initials

S Ishigami,M Sandkvist,F Tsui,E Moore,TA Coleman,DA Lawrence,

For similar enzymes and coenzymes: enzymes: hydrolases: peptide hydrolases: endopeptidases: serine endopeptidases: tissue plasminogen activator research abstracts see: enzymes and coenzymes: enzymes: hydrolases: peptide hydrolases: endopeptidases: serine endopeptidases: tissue plasminogen activator research

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Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Biochemical journal

VOLUME: 402

Page Numbers: 25-34

Journal Abbreviation: Biochem. J.

ISSN: 1470-8728

DAY: 15

MONTH: Feb

YEAR: 2007

Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984726

Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Keywords Mesh Terms:

KEYWORDS: Tissue Plasminogen Activator

MESH TERMS: metabolism

Chemical & Substance for Abstract: Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Information

Substance Name: Tissue Plasminogen Activator

Registry Number: EC 3.4.21.68

Grant and Affiliation Information for Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin.

AFFILIATION: Center for Vascular and Inflammatory Diseases, Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.

Country: England

AGENCY: United States NHLBI

GRANT: HL55747

ACRONYM: HL

MEDLINETA: Biochem J

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