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PMID: 15623578 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

RPTPalpha is essential for NCAM-mediated p59fyn activation and neurite elongation.

The Journal of cell biology ·Vol. 168 ·No. 1 ·2005-01-03 ·Pages 127-39

Bodrikov V, Leshchyns'ka I, Sytnyk V, Overvoorde J, den Hertog J, Schachner M

Abstract

The neural cell adhesion molecule (NCAM) forms a complex with p59fyn kinase and activates it via a mechanism that has remained unknown. We show that the NCAM140 isoform directly interacts with the intracellular domain of the receptor-like protein tyrosine phosphatase RPTPalpha, a known activator of p59fyn. Whereas this direct interaction is Ca2+ independent, formation of the complex is enhanced by Ca2+-dependent spectrin cytoskeleton-mediated cross-linking of NCAM and RPTPalpha in response to NCAM activation and is accompanied by redistribution of the complex to lipid rafts. Association between NCAM and p59fyn is lost in RPTPalpha-deficient brains and is disrupted by dominant-negative RPTPalpha mutants, demonstrating that RPTPalpha is a link between NCAM and p59fyn. NCAM-mediated p59fyn activation is abolished in RPTPalpha-deficient neurons, and disruption of the NCAM-p59fyn complex in RPTPalpha-deficient neurons or with dominant-negative RPTPalpha mutants blocks NCAM-dependent neurite outgrowth, implicating RPTPalpha as a major phosphatase involved in NCAM-mediated signaling.

MeSH Terms
Animals Animals, Newborn CHO Cells Calcium/metabolism Cricetinae Enzyme Activation Membrane Microdomains/metabolism Mice Mice, Knockout Multiprotein Complexes Nerve Tissue Proteins/genetics,metabolism Neural Cell Adhesion Molecules/genetics,metabolism Neurites/metabolism,ultrastructure Protein Isoforms/genetics,metabolism Protein Structure, Tertiary Protein Tyrosine Phosphatases/genetics,metabolism Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-fyn Receptor-Like Protein Tyrosine Phosphatases, Class 4 Receptors, Cell Surface/genetics,metabolism Receptors, Fibroblast Growth Factor/metabolism Signal Transduction/physiology Spectrin/metabolism src-Family Kinases/genetics,metabolism
Chemicals
Multiprotein Complexes Nerve Tissue Proteins Neural Cell Adhesion Molecules Protein Isoforms Proto-Oncogene Proteins Receptors, Cell Surface Receptors, Fibroblast Growth Factor Spectrin Fyn protein, mouse Proto-Oncogene Proteins c-fyn src-Family Kinases Protein Tyrosine Phosphatases Ptpra protein, mouse Receptor-Like Protein Tyrosine Phosphatases, Class 4 Calcium
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bodrikov Vsevolod
Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany.
Leshchyns'ka Iryna
Sytnyk Vladimir
Overvoorde John
den Hertog Jeroen
Schachner Melitta
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200405073
Published
2005-01-03
Epub
2004-00-28
Pages
127-39
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2171675
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200405073 PMC Full Text View journal details
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