Genetic Control of Lithium Sensitivity and Regulation of Inositol Biosynthetic Genes

King, Jason; Keim, Melanie; Teo, Regina; Weening, Karin; Kapur, Mridu; McQuillan, Karina; Ryves, Jonathan; Rogers, B A; Dalton, Emma; Williams, Robin S. B.; Harwood, Adrian J.

doi:10.1371/journal.pone.0011151

Cited by 27 publications

(42 citation statements)

References 47 publications

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“…qPCR was performed exactly as previously described (75). Expression levels were normalized to Ig7 as a loading control and calculated relative to wild-type controls.…”

Section: V-atpasementioning

confidence: 99%

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

Buckley

Gopaldass

Bosmani

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Macropinocytosis is an ancient mechanism that allows cells to harvest nutrients from extracellular media, which also allows immune cells to sample antigens from their surroundings. During macropinosome formation, bulk plasma membrane is internalized with all its integral proteins. It is vital for cells to salvage these proteins before degradation, but the mechanisms for sorting them are not known. Here we describe the evolutionarily conserved recruitment of the WASH (WASP and SCAR homolog) complex to both macropinosomes and phagosomes within a minute of internalization. Using Dictyostelium, we demonstrate that WASH drives protein sorting and recycling from macropinosomes and is thus essential to maintain surface receptor levels and sustain phagocytosis. WASH functionally interacts with the retromer complex at both early and late phases of macropinosome maturation, but mediates recycling via retromer-dependent and -independent pathways. WASH mutants consequently have decreased membrane levels of integrins and other surface proteins. This study reveals an important pathway enabling cells to sustain macropinocytosis without bulk degradation of plasma membrane components.phagocytosis | macropinocytosis | WASH | Dictyostelium | trafficking

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“…qPCR was performed exactly as previously described (75). Expression levels were normalized to Ig7 as a loading control and calculated relative to wild-type controls.…”

Section: V-atpasementioning

confidence: 99%

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

Buckley

Gopaldass

Bosmani

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Subsequent studies demonstrated that PREP was a negative regulator of inositol (1,4,5)-trisphosphate (IP 3 ) synthesis, a Li + sensitive intracellular signalling molecule [9,10] . It was shown in Dictyostelium and in cultured human cells that PREP could act via the enzyme multiple inositol polyphosphate phosphatase (Mipp1) to control gene expression and hence affect the level of the second-messenger IP 3 [9] . This was an indication of the existence of a novel gene regulatory network modulating inositol metabolism and hence Li + sensitivity.…”

mentioning

confidence: 99%

Prolyl Endopeptidase Is Involved in Cellular Signalling in Human Neuroblastoma SH-SY5Y Cells

et al. 2011

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Prolyl endopeptidase (PREP), probably acting through the inositol cycle, has been implicated in memory and learning. However, the physiological role of PREP is unknown. It has been shown that PREP expression, regulated in cerebellar granule cells, has probably a role in cell proliferation and differentiation. Here, we report the levels and subcellular distribution of PREP in human neuroblastoma SH-SY5Y cells in proliferating conditions and under differentiation induced by retinoic acid (RA). We analysed the levels of cell signalling intermediates, growth behavior and gene expression, and differentiation morphology changes, upon PREP inhibition. After induction of differentiation, PREP activity was found decreased in the nucleus but increased to high levels in the cytoplasm, due in part to increased PREP transcription. The levels of inositol (1,4,5)-trisphosphate revealed no correlation with PREP activity, but phosphorylated extracellular signal-regulated kinases 1 and 2 were decreased by PREP inhibition during early stages of differentiation. Morphological evaluation indicated that PREP inhibition retarded the onset of differentiation. PREP activity regulated gene expression of protein synthesis machinery, intracellular transport and kinase complexes. We conclude that PREP is a regulatory target and a regulatory element in cell signalling. This is the first report of a direct influence of a cell signalling molecule, RA, on PREP expression.

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“…In another pathway analysis approach, King et al [43] undertook a genetic screen for Li resistance in the social amoeba Dictyostelium in hopes of deciphering the molecular basis for Li's effectiveness as a mood stabilizer. Prolyl oligopeptidase -an enzyme altered in bipolar disorder patients -is a modulator of Li sensitivity and a negative regulator of inositol(1,4,5)trisphosphate (IP3) synthesis, a Li-sensitive intracellular signal.…”

Section: Expression Studiesmentioning

confidence: 99%

“…Prolyl oligopeptidase -an enzyme altered in bipolar disorder patients -is a modulator of Li sensitivity and a negative regulator of inositol(1,4,5)trisphosphate (IP3) synthesis, a Li-sensitive intracellular signal. The authors showed that in Dictyostelium, as well as in cultured human cells, prolyl oligopeptidase acts via multiple inositol polyphosphate phosphatase (Mipp1) to modulate Li sensitivity through a gene-regulatory network that converges on inositol metabolism [43]. Kubota …”

Section: Expression Studiesmentioning

confidence: 99%

Response to treatment in bipolar disorder

Cruceanu

Alda

Rouleau

et al. 2011

Current Opinion in Psychiatry

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Purpose of review-Bipolar disorder is a complex psychiatric condition that has been shown to carry a great degree of genetic loading. This review addresses current research in the genetics of treatment response in bipolar disorder, with a focus on findings that have shaped our understanding of the changing direction of this field in light of recent technological advancements.Recent findings-The recent publications in bipolar disorder treatment response have helped consolidate or improve upon knowledge of susceptibility loci and genes in the field. There seems to be an increasing trend toward functionally assessing the role played by putative candidate genes and molecular factors modulating expression in bipolar disorder, as well as a movement toward more global, pathway and genome-wide-oriented research.Summary-Genetic and molecular research to date in bipolar disorder treatment response has not completely answered all the lingering questions in the field, but has contributed to the development of a more patient-based understanding of treatment. In order to apply these findings at a clinical level, more comprehensive treatment response studies are imperative, combining recent advances in high-throughput genomics with functional molecular research.

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Genetic Control of Lithium Sensitivity and Regulation of Inositol Biosynthetic Genes

Cited by 27 publications

References 47 publications

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

WASH drives early recycling from macropinosomes and phagosomes to maintain surface phagocytic receptors

Prolyl Endopeptidase Is Involved in Cellular Signalling in Human Neuroblastoma SH-SY5Y Cells

Response to treatment in bipolar disorder

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