PI5P migrates out of the PIP shadow

Devereaux, Kelly

doi:10.1038/embor.2013.2

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…This is also in agreement with our previous finding that ectopic expression of the bacterial enzyme IpgD, which converts PI(4,5)P 2 into PI5P, at least partly rescues the migratory defects in MTMR3 and PIKfyve siRNA-treated cells. 1 , 10 …”

Section: Resultsmentioning

confidence: 99%

Phosphatidylinositol 5-phosphate is a second messenger important for cell migration

Haugsten

Oppelt

Wesche

2013

Communicative & Integrative Biology

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We recently showed that production of phosphatidylinositol 5-phosphate (PtdIns5P or PI5P) upon growth factor stimulation is important for cell migration. However, it was not entirely clear if PI5P itself could be a second messenger in cell migration, or, if it was rather an intermediate for the production of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2 or PI(4,5)P2). Indeed, PI5P can be converted to PI(4,5)P2 by type II PIP4 kinases (PIP4K2s). We therefore decided to knock down PIP4K2α by siRNA to test if further conversion of PI5P to PI(4,5)P2 is important for cell migration. Even though we obtained an efficient knockdown of PIP4K2α in BJ human fibroblasts, we did not observe any change in cell velocity. Conversely, ectopic overexpression of PIP4K2α would consume PI5P to produce PI(4,5)P2 and we found that overexpressing PIP4K2α decreased cell migration speed. Taken together, the data clearly indicate that it is PI5P, and not PI(4,5)P2 produced from PI5P, that is the crucial signaling molecule in cell migration. We conclude, therefore, that PI5P is a true second messenger important for cell migration.

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Section: Resultsmentioning

confidence: 99%

Phosphatidylinositol 5-phosphate is a second messenger important for cell migration

Haugsten

Oppelt

Wesche

2013

Communicative & Integrative Biology

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“…Lysates were extracted and spun, and resulting pellets were washed twice with 0.1 mM EDTA. Samples were then deacylated and separated by high-performance liquid chromatography (Shimadzu Scientific Instruments, Kyoto, Japan) and phosphoinositides identified using deacylated 32 P standards and an online flow scintillation analyzer (B-RAM; IN/US, Conquer Scientific, San Diego, CA) as described ( Devereaux and Di Paolo, 2013 ).…”

Section: Methodsmentioning

confidence: 99%

A role for eisosomes in maintenance of plasma membrane phosphoinositide levels

Fröhlich

Christiano

Olson

et al. 2014

MBoC

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“…Given the considerable amount of evidence indicated above, a legitimate question is why PIKfyve has not been definitively implicated in direct PtdIns5P synthesis [47]. A major obstacle for accepting direct biosynthesis of PtdIns5P by PIKfyve has been an early complementation analysis that found HPLC-undetectable PtdIns5P in a Δ fab1 yeast strain ( Saccharomyces cerevisiae ) ectopically expressing mouse PIKfyve yet the PtdIns(3,5)P 2 was elevated [32].…”

Section: Enzymatic Routes In Intracellular Ptdins5p Productionmentioning

confidence: 99%

PtdIns5P: News and views of its appearance, disappearance and deeds

Shisheva¹

2013

Archives of Biochemistry and Biophysics

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Accumulated evidence indicates that PtdIns5P, one of the seven phosphoinositides, found now to be constitutively present in yeast, plants and metazoa, serves as a signaling molecule to modulate pleiotropic cellular functions in both the nucleus and the cytoplasm. The enzymatic routes in biogenesis of basal PtdIns5P have remained incompletely understood. The role for candidate kinase PIKfyve that is principally involved in PtdIns(3,5)P2 production, has been questioned. In this review article we scrutinize the past obstacles that prevented the definitive implication of PIKfyve in PtdIns5P biosynthesis from PtdIns and focus on the recent pharmacological and genetic advancements that now make this conclusion well supported. We further summarize our current knowledge of the diverse stimuli modulating PtdIns5P levels, binding partners and regulated cellular process, with particular reference to the available mechanistic insights for the relevant signaling pathways.

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PI5P migrates out of the PIP shadow

Abstract: In a recent study published in EMBO reports, the group of Jorgen Wesche identified a new role for PI5P as a positive regulator of cell migration, most likely by facilitating actin cytoskeletal rearrangements.

Cited by 4 publications

References 10 publications

Phosphatidylinositol 5-phosphate is a second messenger important for cell migration

Phosphatidylinositol 5-phosphate is a second messenger important for cell migration

A role for eisosomes in maintenance of plasma membrane phosphoinositide levels

PtdIns5P: News and views of its appearance, disappearance and deeds

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