Cell surface nucleolin on developing muscle is a potential ligand for the axonal receptor protein tyrosine phosphatase‐σ

• Published in: The FEBS journal Vol. 273; no. 20; pp. 4668 - 4681
• Main Authors: Alete, Daniel E., Weeks, Mark E., Hovanession, Ara G., Hawadle, Muhamed, Stoker, Andrew W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2006; Wiley
• Subjects: affinity chromatography; Amino Acid Sequence; Animals; axon targeting; Axons - metabolism; Biochemistry, Molecular Biology; Cells, Cultured; Chick Embryo; Lactoferrin - metabolism; Life Sciences; Ligands; Membrane Proteins - metabolism; Molecular Sequence Data; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - growth & development; Muscle, Skeletal - metabolism; Nucleolin; Peptides - metabolism; Phosphoproteins - metabolism; Protein Binding; Protein Tyrosine Phosphatases - metabolism; RAP assay; receptor protein tyrosine phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 2; RNA-Binding Proteins - metabolism
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2006.05471.x

Reversible tyrosine phosphorylation, catalyzed by receptor tyrosine kinases and receptor tyrosine phosphatases, plays an essential part in cell signaling during axonal development. Receptor protein tyrosine phosphatase‐σ has been implicated in the growth, guidance and repair of retinal axons. This phosphatase has also been implicated in motor axon growth and innervation. Insect orthologs of receptor protein tyrosine phosphatase‐σ are also implicated in the recognition of muscle target cells. A potential extracellular ligand for vertebrate receptor protein tyrosine phosphatase‐σ has been previously localized in developing skeletal muscle. The identity of this muscle ligand is currently unknown, but it appears to be unrelated to the heparan sulfate ligands of receptor protein tyrosine phosphatase‐σ. In this study, we have used affinity chromatography and tandem MS to identify nucleolin as a binding partner for receptor protein tyrosine phosphatase‐σ in skeletal muscle tissue. Nucleolin, both from tissue lysates and in purified form, binds to receptor protein tyrosine phosphatase‐σ ectodomains. Its expression pattern also overlaps with that of the receptor protein tyrosine phosphatase‐σ‐binding partner previously localized in muscle, and nucleolin can also be found in retinal basement membranes. We demonstrate that a significant amount of muscle‐associated nucleolin is present on the cell surface of developing myotubes, and that two nucleolin‐binding components, lactoferrin and the HB‐19 peptide, can block the interaction of receptor protein tyrosine phosphatase‐σ ectodomains with muscle and retinal basement membranes in tissue sections. These data suggest that muscle cell surface‐associated nucleolin represents at least part of the muscle binding site for axonal receptor protein tyrosine phosphatase‐σ and that nucleolin may also be a necessary component of basement membrane binding sites of receptor protein tyrosine phosphatase‐σ.