Disease relevance of PPP1R9B

• Moderate instability of the trinucleotide repeat in spino bulbar muscular atrophy [1].
• The validity of this approach is supported by the detection of nervous system-specific genes (e.g., glial fibrillary acid protein) and genes known to show trinucleotide expansions in disease (e.g., AAD10 associated with spino cerebellar ataxia type 2) [2].
• CSF pNfH levels above the reference limit were observed in patients with encephalitis, encephalomyelitis, hydrocephalus, subarachnoid haemorrhage, spino-muscular atrophy, stroke and cancer with both methods agreeing in all cases [3].
• Pelvic morphology and spino-pelvic balance are abnormal in developmental spondylolisthesis [4].
• The case of clinically benign spino-cerebral meningitis in the development of cranial basis neoplasm [5].

Psychiatry related information on PPP1R9B

• Reduced spinophilin but not microtubule-associated protein 2 expression in the hippocampal formation in schizophrenia and mood disorders: molecular evidence for a pathology of dendritic spines [6].

High impact information on PPP1R9B

• Specifically, we examined whether the D1 dopamine receptor-interacting protein calcyon and the D2 dopamine receptor-interacting proteins filamin-A and spinophilin are affected in the dorsolateral prefrontal cortex of patients with schizophrenia [7].
• Adrenergic modulation of NMDA receptors in prefrontal cortex is differentially regulated by RGS proteins and spinophilin [8].
• These data demonstrate a role for spinophilin in cell growth and suggest that ARF and spinophilin could act in partially overlapping pathways [9].
• We report here that the human homologue of spinophilin/neurabin II, a regulatory subunit of protein phosphatase 1 catalytic subunit specifically interacts with ARF, both in yeast and in mammalian cells [9].
• CONCLUSIONS: Decreased spinophilin but unchanged MAP2 expression provides molecular evidence for a hippocampal dendritic pathology in schizophrenia that preferentially affects the spines [6].

Biological context of PPP1R9B

• Association of Dcx with F-actin is regulated by site-specific phosphorylation and by neurabin II, an F-actin binding protein that also binds to Dcx [10].
• In response to a defined dose of letrozole, the downregulation of spinophilin expression was significantly stronger in CA1 neurons and in granule cells, than in cells of the CA3 region in slice cultures [11].
• Evoked potentials from the lower urinary tract. II. The spino-cortical neuraxis. A methodological study [12].

Anatomical context of PPP1R9B

• RESULTS: The patients with schizophrenia had lower levels of spinophilin mRNA in CA4 (hilus), CA3, the subiculum, and the entorhinal cortex than did the normal comparison subjects [6].
• Neurabin II mediates doublecortin-dephosphorylation on actin filaments [10].
• We suggest that a dynamic regulation of Dcx mediated by neurabin II regulates the translocation of Dcx from F-actin to microtubules and vice versa [10].
• In this study, we sought to determine the structural basis for the targeting of spinophilin to dendritic spines [13].
• Spinophilin is enriched in dendritic spines, small protrusions of the postsynaptic membrane along the length of the dendrite that contain the majority of excitatory synapses [13].

Associations of PPP1R9B with chemical compounds

• Spinophilin binds to protein phosphatase 1 with high affinity and targets it to dendritic spines, therefore placing it in proximity to regulate glutamate receptor activity [13].
• Conversely, 0.1 microM haloperidol decreased spinophilin protein by 40%, caused a 25% decrease in shank1a puncta and reduced the numbers of filopodia [14].
• Further analyses demonstrated that ICI 182,780 induced significant activation of extracellular signal-regulated kinase 1/2 and Akt (protein kinase B) and significantly increased expression of spinophilin and Bcl-2, with efficacy comparable with neurons treated with 17beta-estradiol [15].

Physical interactions of PPP1R9B

• By contrast, abolishing PP1 binding to neurabin II maintains phosphorylation levels of Dcx, leading to a retention of Dcx at F-actin [10].

Regulatory relationships of PPP1R9B

• Spinophilin regulates also seven-transmembrane receptor signalling and may provide a link between some of these receptors and intracellular mitogenic signalling events dependent on p70(S6) kinase and Rac G protein-GEF [16].

Other interactions of PPP1R9B

• We show here that neurabin II mediates dephosphorylation of Dcx by protein phosphatase 1 (PP1) [10].
• More specifically, S100A8/A9 appeared in the majority within the spino-cellular layer and located extracellularly within the desmosomes [17].
• Next, we treated hippocampal cell cultures with letrozole, an aromatase inhibitor, which resulted in a dose-dependent decrease in the release of 17beta-estradiol into the medium and in a dose-dependent downregulation of spinophilin and synaptophysin expression in dissociated hippocampal neurons [11].
• Quantitative immunohistochemistry revealed a dose-dependent downregulation of spinophilin, a spine marker, and of synaptophysin, a presynaptic marker, in the hippocampus [18].
• The solid tumors were genital cancers, malignant melanoma, spino-cellular carcinoma, thyroid cancer, hemangiosarcoma [19].

Analytical, diagnostic and therapeutic context of PPP1R9B

• We describe a gastric non neoplastic ulceration that arose late after six years from an esophagectomy, with an end-side cervical esophagogastrostomy, for a spino-cellular carcinoma [20].

References