Disease relevance of Ptprs

• By approximately three weeks of age, most remaining Ptprs-/- mice died from a wasting syndrome with atrophic intestinal villi [1].
• Since low dose injection of growth hormone (GH) normalized the response to exogenous insulin in RPTPsigma-/- mice, we propose that the insulin hypersensitivity observed in RPTPsigma-/- mice is secondary to their neuroendocrine dysplasia and GH/IGF-1 deficiency [2].
• Dorsal root ganglion (DRG) neurons, which highly express endogenous N-cadherin and PTPsigma, exhibited a faster growth rate in the knockout mice than in the sibling controls when grown on laminin or N-cadherin substrata [3].

Psychiatry related information on Ptprs

• The surviving Ptprs-/- mice demonstrated stunted growth, developmental delays and severe neurological defects including spastic movements, tremor, ataxic gait, abnormal limb flexion and defective proprioception [1].

High impact information on Ptprs

• Moreover, peripheral nerve electrophysiological analysis revealed slower conduction velocity in Ptprs-/- mice relative to wild-type or heterozygous animals, associated with an increased proportion of slowly conducting, small-diameter myelinated fibres and relative hypomyelination [1].
• Histopathology of brain sections revealed reduction and hypocellularity of the posterior pituitary of Ptprs-/- mice, as well as a reduction of approximately 50-75% in the number of choline acetyl transferase-positive cells in the forebrain [1].
• Neuronal defects and posterior pituitary hypoplasia in mice lacking the receptor tyrosine phosphatase PTPsigma [1].
• On the basis of its expression and homology with the Drosophila melanogasterorthologues DPTP99 and DPTP100A (refs 5,6), which have roles in the targeting of axonal growth cones, we hypothesized that PTP-sigma may also have a modulating function in cell-cell interactions, as well as in axon guidance during mammalian embryogenesis [4].
• We have discovered that a member of the dual-specific protein tyrosine phosphatase (DS-PTP) family, PTPMT1 (PTP localized to the Mitochondrion 1) resides nearly exclusively in mitochondria [5].

Biological context of Ptprs

• Developmental expression of the cell adhesion molecule-like protein tyrosine phosphatases LAR, RPTPdelta and RPTPsigma in the mouse [6].
• Despite increased whole-body insulin sensitivity, tyrosine phosphorylation of the IR was not increased in muscle of RPTPsigma-/- animals, as would be expected in insulin-sensitive animals [2].
• We established neural stem cell cultures, grown as neurospheres, from the SVZ of PTPsigma knockout mice and sibling controls to determine if PTPsigma influences the generation and the phenotype of the neuronal, astrocyte and oligodendrocyte cell lineages [7].
• The 627-amino acid cytoplasmic region of RPTP-sigma consists of two catalytic domains oriented in tandem [8].
• The gene for RPTP-sigma has been mapped to distal chromosome 17 in the mouse [8].

Anatomical context of Ptprs

• CONCLUSION: Our results imply a specific role for PTPsigma in the neuronal lineage, particularly in the form of inhibitory influences on neurite outgrowth, and demonstrate a role for tyrosine phosphatases in neuronal stem cell differentiation [7].
• While no apparent differences were observed in developing neurospheres or in the astrocytes and oligodendrocytes from the PTPsigma knockout mice, the neuronal migration patterns and neurites were altered when studied in culture [7].
• A novel transmembrane receptor protein tyrosine phosphatase-sigma (RPTP-sigma) was cloned from a rat brain stem cDNA library [8].
• Within the latter structure, RPTP-sigma is present in the pyramidal cell layer and granular layer of the dentate gyrus [8].
• During embryonic development, RPTP-sigma is expressed extensively in the central and peripheral nervous systems, including the trigeminal and dorsal root ganglia as well as the retina [8].

Associations of Ptprs with chemical compounds

• We show that RPTPsigma-/- knockout mice have reduced plasma glucose and insulin concentrations in the fasted state compared with their wild-type siblings [2].

Other interactions of Ptprs

• These results suggest that the elevated tyrosine phosphorylation of N-cadherin in the PTPsigma(-/-) mice likely disrupted N-cadherin function, resulting in accelerated DRG nerve growth [3].
• RPTP-sigma/delta double mutants exhibit severe muscle dysgenesis and severe loss of motoneurons in the spinal cord [9].

Analytical, diagnostic and therapeutic context of Ptprs

• To study the role of PTPsigma in mouse development, we inactivated Ptprs by gene targeting [1].
• Using RNA in situ hybridization we compared the expression patterns of the cell adhesion molecule-like receptor-type protein tyrosine phosphatases LAR, RPTP sigma and RPTP sigma during mouse development [6].
• Northern blot analyses indicate that RPTP-sigma is highly expressed in the brain as two major transcripts of 5.7 and 6.9 kilobases (kb) [8].
• Transfection of RPTP-sigma cDNA into human embryonic kidney 293 cells results in the synthesis of a protein with an apparent molecular mass of 200 kDa as detected by immunoprecipitation and immunoblot analyses using polyclonal antibodies against the FNIII-like repeats present in the extracellular domain of RPTP-sigma [8].
• Immunocytochemical examination of wild-type neurons in cell culture showed RPTPsigma protein in the growth cone [10].

References