Differential expression of receptor protein tyrosine phosphatases accompanies the reorganisation of the retina upon laser lesion

摘要

The regulation of protein phosphorylation plays an essential role in virtually all aspects of eukaryotic development. Beginning with the regulation of the cell cycle to cellular proliferation and differentiation, the delicate balance between the phosphorylating activity of kinases and the dephosphorylation by phosphatases controls the outcome of many signal transduction cascades. The generation of cellular diversity occurs in an environment that is structured by the extracellular matrix (ECM) which forms a surrounding niche for stem and progenitor cells. Cell–cell and cell–matrix interactions elicit specific signaling pathways that control cellular behavior. In pathological situations such as neural degenerating diseases, gene expression patterns and finally the composition of the ECM change dramatically. This leads to changes of cell behavior and finally results in the failure of regeneration and functional restoration in the adult central nervous system. In order to study the roles of tyrosine phosphatases and ECM in this context, we analyzed the effects of laser-induced retinal injury on the regulation of the receptor protein tyrosine phosphatases (RPTP) RPTPBr7, Phogrin and RPTPβ/ζ. The latter occurs in several isoforms, including the soluble released chondroitin sulfate proteoglycan phosphacan that is expressed in the developing retina. The receptor variants RPTPβ/ζ_long and RPTPβ/ζ_short may serve as receptors of tenascin-proteins and serve as modulators of cell intrinsic signaling in response to the ECM. Using quantitative real-time RT-PCR analysis, we show here a time-dependent pattern of gene expression of these molecules following laser lesions of the retina. Keywords Receptor protein tyrosine phosphatases - Phogrin - RPTPBr7 - RPTPβ/ζ isoforms - Neural regeneration - Retinal laser lesion - Extracellular matrix - Tenascin-C - Phosphacan - Neuron–glia interactions - Regeneration Manuela Besser and Andrea Horvat-Bröcker have contributed equally.