Differential expression of phosphacan/RPTPβ isoforms in the developing mouse visual system

Abstract

The chondroitin sulfate proteoglycan DSD-1-PG/phosphacan represents one of four splice variants of receptor-protein-tyrosine-phosphatase-beta/zeta (RPTPbeta/zeta). This receptor is expressed by glial cells and occurs in two isoforms, RPTPbeta(long) and RPTPbeta(short). The secreted forms phosphacan and phosphacan short isoform (PSI) bind to extracellular matrix and adhesion molecules and might mediate astroglial effects on neuronal differentiation. Phosphacan and RPTPbeta(long) both carry the DSD-1 epitope, a glycosaminoglycan modification that is involved in stimulating neurite outgrowth of embryonic rat mesencephalic and hippocampal neurons in a polycationic environment. Additionally, phosphacan inhibits neurite outgrowth of embryonic DRG neurons in the presence of laminin. In the light of these functional properties we examined the expression patterns of the DSD-1 epitope and phosphacan isoforms in the developing mouse visual system. During retinal development the DSD-1 epitope appears around embryonic day (E)13, peaks around postnatal day (P)6, and is downregulated from P9 to adolescence. By comparison, the phosphacan core protein is first detectable at E12, reaches maximal levels around P14, and persists, although at lower levels, to adulthood. The DSD-1 epitope is restricted to the nerve fiber and the inner plexiform layers. In contrast, the phosphacan core protein immunoreactivity extends from the nerve fiber layer to the outer plexiform layer. The level of expression of the phosphacan/RPTPbeta gene was investigated by reverse-transcriptase polymerase chain reaction. These experiments suggest that there is a shift in the expression patterns of the different phosphacan/RPTPbeta isoforms during late embryonic and postnatal development. In situ hybridization experiments support the conclusion that at least one of the phosphacan/RPTPbeta isoforms in the retina is expressed by neurons.

Expression and localization of receptor protein tyrosine phosphatase β and its ligand pleiotrophin in the submandibular gland of mice

“…In the development of the central nervous system, including that of the retina, all types of RPTPb seem to have similar biological roles. 43 Interestingly, similar to the present case, osteoblasts specifically express the short receptor type of RPTPb (RPTPb-S), the deficiency of which causes abnormality in bone remodelling in mice. 41 Several ligands are known to bind to RPTPb, including the extracellular matrix protein tenastin, the cell adhesion molecules contactin and N-CAM, and the growth factor PTN and midkine.…”

Tenascin C regulates proliferation and differentiation processes during embryonic retinogenesis and modulates the de-differentiation capacity of Müller glia by influencing growth factor responsiveness and the extracellular matrix compartment

“…In a first step, the expression of the Tnc interaction partners Phosphacan and RPTPb/z-long was investigated. These proteins also occur as chondroitin sulfate proteoglycans (CSPGs) that bear a specific carbohydrate motif recognized by the monoclonal antibody 473HD (Barnea et al, 1994;Grumet et al, 1994;Klausmeyer et al, 2007) and is expressed by radial glia neural stem/progenitor cells (Horvat-Brocker et al, 2008;von Holst et al, 2006). Immunohistochemical stainings, the quantification of immunopositive single cells and Western blotting evidenced an up-regulation of this CS-epitope in the Tnc-deficient tissue.…”

“…7a-f). This unique epitope is specifically localized on chondroitin sulfate (CS) side chains attached to the core proteins of the above mentioned proteoglycans Klausmeyer et al, 2007;von Holst et al, 2006). For the quantitative evaluation of this phenotype, further immunocytochemical stainings with the 473HD antibody on acutely dissociated living cells were performed.…”

“…Investigations of a Tnc À / À mouse strain (Forsberg et al, 1996;Saga et al, 1992) revealed subtle alterations in non-neural and neural tissues, resulting in several neurological defects, inhibition of regeneration/plasticity and de-regulated morphogenesis (Evers et al, 2002;Faissner, 1997;Fukamauchi et al, 1996;Fukamauchi et al, 1997;Garcion et al, 2004;Irintchev et al, 2005;Jones and Jones, 2000a). Immunohistochemical analysis revealed that Tnc is expressed in the retina in a spatiotemporal pattern (Klausmeyer et al, 2007;Lara et al, 2010). Investigations concerning the influence of Tnc during retinogenesis remained an outstanding question.…”

Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

“…Dimerization following Pleiotrophin binding inactivates the phosphatase domains and thereby increases the phosphorylation state of downstream factors like Adducin, a cytoskeletal protein (Pariser et al, 2005b). Other extracellular interaction partners are TN-C, Contactin/F3/F11, the cell adhesion molecules L1CAM and NCAM (Klausmeyer et al, 2007), and FGF (Milev et al, 1998b). RPTPβ isoforms are regulated after knife lesion of the cerebral cortex (Dobbertin et al, 2003), striatal stab wound (Barker et al, 1996), and after retinal laser lesion (Besser et al, 2009) and are critical for recovery (Harroch et al, 2002).…”