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PMID: 9321387 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The chemorepulsive activity of secreted semaphorins is regulated by furin-dependent proteolytic processing.

The EMBO journal ·Vol. 16 ·No. 20 ·1997-10-15 ·Pages 6077-86

Adams RH, Lohrum M, Klostermann A, Betz H, Püschel AW

Abstract

The semaphorins are a large group of cell surface and secreted proteins implicated in axonal pathfinding. Here we show that the secreted mouse semaphorin D (SemD) is synthesized as an inactive precursor (proSemD) and becomes repulsive for sensory and sympathetic neurites upon proteolytic cleavage. ProSemD processing can be blocked completely by an inhibitor selective for furin-like endoproteases or mutagenesis of three conserved dibasic cleavage sites. Its C-terminal pro-peptide contains a processing signal that is essential for SemD to acquire its full repulsive activity. SemD processing is regulated during the embryonic development of the mouse and determines the magnitude of its repulsive activity. Similarly to SemD, the secreted semaphorins SemA and SemE display repulsive properties that are regulated by processing. Our data suggest that differential proteolytic processing determines the repulsive potency of secreted semaphorins and implicate proteolysis as an important regulatory mechanism in axonal pathfinding.

MeSH Terms
Animals Carrier Proteins Cell Communication Chick Embryo Coculture Techniques DNA Mutational Analysis Furin Gene Expression Regulation, Developmental Glycoproteins/metabolism,pharmacology Mice Models, Biological Nerve Growth Factors/metabolism,pharmacology Nerve Tissue Proteins Neurites/drug effects Protein Precursors/metabolism Protein Processing, Post-Translational Semaphorin-3A Subtilisins/metabolism
Chemicals
Carrier Proteins Glycoproteins Nerve Growth Factors Nerve Tissue Proteins Protein Precursors Sema3a protein, mouse Semaphorin-3A semaphorin A(V) Subtilisins Furin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Adams R H
Abteilung Neurochemie, Max-Planck-Institut für Hirnforschung, Deutschordenstr. 46, D-60528 Frankfurt/Main, Germany.
Lohrum M
Klostermann A
Betz H
Püschel A W
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.20.6077
Published
1997-10-15
Pages
6077-86
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1326291
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/16.20.6077 PMC Full Text View journal details
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