Document Detail

The extracellular matrix proteoglycan perlecan facilitates transmembrane semaphorin-mediated repulsive guidance.
MedLine Citation:
PMID:  23028146     Owner:  NLM     Status:  MEDLINE    
The Drosophila transmembrane semaphorin-1a (Sema-1a) is a repulsive guidance cue that uses the Plexin A (PlexA) receptor during neural development. Sema-1a is required in axons to facilitate motor axon defasciculation at guidance choice points. We found that mutations in the trol gene strongly suppress Sema-1a-mediated repulsive axon guidance. trol encodes the phylogenetically conserved secreted heparan sulfate proteoglycan (HSPG) perlecan, a component of the extracellular matrix. Motor axon guidance defects in perlecan mutants resemble those observed in Sema-1a- and PlexA-null mutant embryos, and perlecan mutants genetically interact with PlexA and Sema-1a. Perlecan protein is found in both the CNS and the periphery, with higher expression levels in close proximity to motor axon trajectories and pathway choice points. Restoring perlecan to mutant motor neurons rescues perlecan axon guidance defects. Perlecan augments the reduction in phospho-focal adhesion kinase (phospho-FAK) levels that result from treating insect cells in vitro with Sema-1a, and genetic interactions among integrin, Sema-1a, and FAK in vivo support an antagonistic relationship between Sema-1a and integrin signaling. Therefore, perlecan is required for Sema-1a-PlexA-mediated repulsive guidance, revealing roles for extracellular matrix proteoglycans in modulating transmembrane guidance cue signaling during neural development.
Joong Youn Cho; Kayam Chak; Benjamin J Andreone; Joseph R Wooley; Alex L Kolodkin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Genes & development     Volume:  26     ISSN:  1549-5477     ISO Abbreviation:  Genes Dev.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8711660     Medline TA:  Genes Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2222-35     Citation Subset:  IM    
The Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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MeSH Terms
Drosophila Proteins / genetics,  metabolism*
Drosophila melanogaster / embryology*,  genetics,  metabolism
Extracellular Matrix / metabolism*
Focal Adhesion Protein-Tyrosine Kinases / metabolism
Gene Expression Profiling
Gene Expression Regulation, Enzymologic
Heparan Sulfate Proteoglycans / genetics,  metabolism*
Motor Neurons / cytology*,  metabolism
Semaphorins / metabolism*
Signal Transduction
Grant Support
Reg. No./Substance:
0/Drosophila Proteins; 0/Heparan Sulfate Proteoglycans; 0/Semaphorins; 0/trol protein, Drosophila; EC Adhesion Protein-Tyrosine Kinases

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