Induction of Neurite Outgrowth through Contactin and Nr-CAM by Extracellular Regions of Glial Receptor Tyrosine Phosphatase β

Abstract

Receptor protein tyrosine phosphatase β (RPTPβ) is expressed as soluble and receptor forms with common extracellular regions consisting of a carbonic anhydrase domain (C), a fibronectin type III repeat (F), and a unique region called S. We showed previously that a recombinant Fc fusion protein with the C domain (βC) binds to contactin and supports neuronal adhesion and neurite growth. As a substrate, βCFS was less effective in supporting cell adhesion, but it was a more effective promoter of neurite outgrowth than βCF. βS had no effect by itself, but it potentiated neurite growth when mixed with βCF. Neurite outgrowth induced by βCFS was inhibited by antibodies against Nr-CAM and contactin, and these cell adhesion molecules formed a complex that bound βCFS. NIH3T3 cells transfected to express βCFS on their surfaces induced neuronal differentiation in culture. These results suggest that binding of glial RPTPβ to the contactin/Nr-CAM complex is important for neurite growth and neuronal differentiation.

A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells

“…Since the discovery of the interactions between PTPRZ and CNTN1 (5), the prevailing notion has been that the transmembrane form of PTPRZ expressed on glial cells interacts in trans with CNTN1 at the surface of axons, promoting glial adhesion and neurite outgrowth (20,28). Our results demonstrate that soluble PTPRZ modulates OPC proliferation via CNTN1 expressed at the surface of OPCs.…”

“…However, these regions are not necessary to bind to CNTN1 (Fig. 2) (20), which suggests that they may help recruit additional molecules at the surface of OPCs. Interestingly, proteins such as the growth factor pleiotrophin, the extracellular matrix glycoproteins tenascin-C and tenascin-R (TNR), and the cell adhesion molecules L1, NrCAM, and CNTN2, have been shown to interact with the FNIII and the spacer regions of PTPRZ (6).…”

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

“…[52][53][54][55][56] PTPRZ1 gene products are expressed from early developmental to adulthood in glial cells 47,[57][58][59] as well as in certain population of neurons [60][61][62][63] and are implicated in neuron-glial cell interactions that involve on bi-directional signaling, including myelination and node of Ranvier formation, through interactions with neuronal cell adhesion molecules. 55,56 Interestingly, in situ hybridization analysis has shown that PTPRZ1 is expressed in the subventricular zone of the lateral ventricles in early embryos and in adults, in the subgranular zone in the dentate gyrus of the hippocampus of adults, 57,64 and in adult glial progenitor cells, 65 suggesting that PTPRZ1 also has a function in adult stem/progenitor cells. In addition, it has been shown that inhibition of PTPRZ1 expression or inhibition of RPTPb activity in adult glial progenitors leads to their differentiation into mature oligodendrocytes, 65 supporting a role for RPTPb activity in the maintenance of glial progenitors in an undifferentiated state.…”

Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells

“…Total IgGs were purified from plasma from all SSc patients and from two normal volunteers, by use of recombinant protein G-Sepharose 4B conjugate (Zymed Laboratories, San Fran-cisco, CA) and disposable spin-out columns (G Biosciences, Maryland Heights, MO) as previously described (42). Briefly, rec-protein G-Sepharose 4B conjugate was diluted 1:10 in 20 mM sodium phosphate pH 7.0, loaded on spin-out columns, and allowed to drain.…”