Phosphacan short isoform, a novel non-proteoglycan variant of phosphacan/receptor protein tyrosine phosphatase-beta, interacts with neuronal receptors and promotes neurite outgrowth.
Phosphacan, one of the principal proteoglycans in the extracellular matrix of the central nervous system, is implicated in neuron-glia interactions associated with neuronal differentiation and myelination. We report here the identification of a novel truncated form of phosphacan, phosphacan short isoform (PSI), that corresponds to the N-terminal carbonic anhydrase- and fibronectin type III-like domains and half of the spacer region. The novel cDNA transcript was isolated by screening of a neonatal brain cDNA expression library using a polyclonal antibody raised against phosphacan. Expression of this transcript in vivo was confirmed by Northern blot hybridization. Analysis of brain protein extracts reveals the presence of a 90-kDa glycosylated protein in the phosphate-buffered saline-insoluble 100000 x g fraction that reacts with antisera against both phosphacan and a recombinant PSI protein and that has the predicted N-terminal sequence. This protein is post-translationally modified with oligosaccharides, including the HNK-1 epitope, but, unlike phosphacan, it is not a proteoglycan. The expression of the PSI protein varies during central nervous system development in a fashion similar to that observed for phosphacan, being first detected around embryonic day 16 and then showing a dramatic increase in expression to plateau around the second week post-natal. Both the native and recombinant PSI protein can interact with the Ig cell adhesion molecules, F3/contactin and L1, and in neurite outgrowth assays, the PSI protein can promote outgrowth of cortical neurons when used as a coated substrate. Hence, the identification of this novel isoform of phosphacan/receptor protein tyrosine phosphatase-beta provides a new component in cell-cell and cell-extracellular matrix signaling events in which these proteins have been implicated.
Garwood
Jeremy
J
Laboratoire de Neurobiologie du Développement et de la Régénération, CNRS Centre de Neurochimie, 67084 Strasbourg, France. garwood@neurochem.u-strasbg.fr
Heck
Nicolas
N
Reichardt
Frank
F
Faissner
Andreas
A
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000196:embryology; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004622:Embryo, Mammalian; D014644:Genetic Variation; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D016501:Neurites; D009474:Neurons / Q000737:chemistry* / Q000648:ultrastructure; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases; D012333:RNA, Messenger / Q000032:analysis / Q000302:isolation & purification; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D011956:Receptors, Cell Surface / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017027:Protein Tyrosine Phosphatases; C516896:Ptprz1 protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5