Cortical neurons express PSI, a novel isoform of phosphacan/RPTPbeta

Abstract

Phosphacan is a chondroitin sulfate proteoglycan representing the secreted extracellular part of a transmembrane receptor protein tyrosine phosphatase (RPTP-beta). These isoforms have been implicated in cell-extracellular matrix signaling events associated with myelination, axon growth, and cell migration in the developing central nervous system and may play critical roles in the context of brain pathologies. Recently, we have reported the identification of a new isoform of phosphacan, the phosphacan short isoform (PSI), the expression of which peaks in the second postnatal week. PSI interacts with the neuronal receptors L1 and F3/contactin and can promote neurite growth of cortical neurons. In this study, we have assessed, by in situ hybridization, the expression profile of PSI in the rat brain at postnatal day 7. PSI is largely expressed in the gray matter of the developing cerebral cortex in which it colocalizes with phosphacan, whereas the expression of RPTPbeta receptor forms is restricted to the ventricular area in which PSI has not been observed. Neurons from all layers of the cortex express PSI. In the cerebellum, on the other hand, no expression of PSI has been detected, although the other phosphacan/RPTP-beta isoforms show strong PSI expression here. Overall, our study suggests that PSI is expressed during the postnatal period in differentiated neurons of the cortex but is absent from structures in which proliferation and migration occur. The significance of these observations is discussed in the context of previous models of phosphacan/RPTP-beta functions.

The mouse F3/contactin glycoprotein

“…[105][106][107][108] Within the node, Na + channels also undergo cis-association with the Ig superfamily glycoprotein Nf186, [108][109][110] and complexes between F3/Contactin, Nf186 and Na + channels then interact in trans with glial components as Tenascin-C, Tenascin R, [111][112][113][114][115] receptor protein tyrosine phosphatase β (RPTP β) and its Phosphocan derivative. 116,117 Together, these data support the view that F3/Contactin is a relevant component of the nodal region, in which it undergoes association with and modulates the topography of molecules of critical relevance for neuronal function as the Na + channels.…”

Molecular dissection of NRG1-ERBB4 signaling implicates PTPRZ1 as a potential schizophrenia susceptibility gene

“…43 There are four splicing isoforms of PTPRZ1, two of which are transmembrane receptor forms (RPTPb, short and long) and the other two are soluble forms that lack both a transmembrane region and tyrosine phosphatase activity (phosphacan, short and long). [44][45][46][47][48][49][50] The extracellular region of PTPRZ1 consists of several modular structural domains, including a carbonic anhydrase domain, a fibronectin type III repeat, a spacer domain (all of which are present in all four isoforms), and a region containing B860 amino acids (that is missing in the RPTPb and phosphacan short forms) where several glycosaminoglycan chains can be attached. 44 The carbonic anhydrase domain interacts with the cell recognition molecule contactin, 51 whereas the spacer region can interact with several other cell adhesion molecules including NrCAM, L1CAM, NCAM, contactin-1 and contactin-2/TAG-1.…”

Receptor Type Protein Tyrosine Phosphatase ζ-Pleiotrophin Signaling Controls Endocytic Trafficking of DNER That Regulates Neuritogenesis

“…While normal DNER was actively endocytosed and inhibited the retinoic-acid-induced neurite outgrowth of Neuro-2A cells, pleiotrophin stimulation increased the tyrosine phosphorylation level of DNER and suppressed the endocytosis of this protein, which led to the reversal of this inhibition, thus allowing neurite extension. These observations suggest that pleiotrophin-PTP signaling controls subcellular localization of DNER and thereby regulates neuritogenesis.Protein tyrosine phosphatase (PTP), also known as RPTP/␤, is a receptor type protein tyrosine phosphatase that is synthesized as a chondroitin sulfate proteoglycan (12,16,17,21,28,32). There are three major splice variants of this molecule, the full-length form (PTP-A), the short receptor form (PTP-B), and the secreted form (phosphacan) (Fig.…”

“…Protein tyrosine phosphatase (PTP), also known as RPTP/␤, is a receptor type protein tyrosine phosphatase that is synthesized as a chondroitin sulfate proteoglycan (12,16,17,21,28,32). There are three major splice variants of this molecule, the full-length form (PTP-A), the short receptor form (PTP-B), and the secreted form (phosphacan) (Fig.…”