Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum

Barlow, Christy A.; Laishram, Rakesh S.; Anderson, Richard A.

doi:10.1016/j.tcb.2009.09.009

Cited by 124 publications

(147 citation statements)

References 113 publications

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“…Figure 3 and data not shown). We also confirmed that both PtdIns(4,5)P2 and PtdIns (3,4,5)P3 are substrates for the murine Inpp5k protein (Suppl. informations and Suppl.…”

Section: Results: Production and Characterization Of Inpp5k Transgenisupporting

confidence: 77%

“…Running title: Inpp5k and the control of renal water transport Eileen Pernot 1,2,7 , Sara Terryn 4,7 , Siew Chiat Cheong Inositol Phosphatase, and Pps, for Putative Phosphatase) [2,7,30,32,33]. These enzymes tightly control the level of the above-mentioned phosphoinositides in a tissue-, cellular-, subcellular-and signalling cascade-specific way.…”

Section: The Inositol Inpp5k 5-phosphatase Affects Osmoregulation Thrmentioning

confidence: 99%

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The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

Pernot

Terryn

Cheong

et al. 2011

Pflugers Arch - Eur J Physiol

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Inositol Inpp5k (or Pps, SKIP) is a member of the inositol polyphosphate 5-phosphatases family with a poorly characterized function in vivo. In this study, we explored the function of this inositol 5-phosphatase in mice and cells overexpressing the 42-kDa mouse Inpp5k protein. Inpp5k transgenic mice present defects in water metabolism characterized by a reduced plasma osmolality at baseline, a delayed urinary water excretion following a water load, and an increased acute response to vasopressin. These defects are associated with the expression of the Inpp5k transgene in renal collecting ducts and with alterations in the arginine vasopressin/aquaporin-2 signalling pathway in this tubular segment. Analysis in a mouse collecting duct mCCD cell line revealed that Inpp5k overexpression leads to increased expression of the arginine vasopressin receptor type 2 and increased cAMP response to arginine vasopressin, providing a basis for increased aquaporin-2 expression and plasma membrane localization with increased osmotically induced water transport. Altogether, our results indicate that Inpp5k 5-phosphatase is important for the control of the arginine vasopressin/aquaporin-2 signalling pathway and water transport in kidney collecting ducts. [13,17, 29, 40]. It also regulates the activity of many ion channels and transporters [35,36]. PtdIns(4,5)P2 is mainly localized in the inner leaflet of plasma membranes, but smaller pools have been detected in intracellular membranes, including Golgi, endoplasmic reticulum, endosomes and lamellipodia [13]. Mechanistically, a very large number of proteins are recruited to PtdIns(4,5)P2 via pleckstrin homology (PH), phagocyte oxidase (PX), Fab1p, YOTB, Vac1p and EEA1 (FYVE), epsin N-terminal homology (ENTH) domains or through small patches of basic amino acids [13,18, 28]. PtdIns(4,5,)P2 also serves as precursor of five essential signalling molecules: diacylglycerol, inositol (1,4,5)-trisphosphate, PtdIns4P, PtdIns5P and PtdIns(3,4,5)P3 [13,17]. In non stimulated cells, PtdIns(3,4,5)P3 levels are very low in the plasma membrane, reaching ~0.1% of the level of PtdIns(4,5)P2 [13,17]. Upon cell activation, PtdIns(3,4,5)P3 levels are transiently increased by a factor ranging from 2-to 100-fold. This phosphoinositide is implicated in the control of cell survival, growth and proliferation, resistance to apoptosis, regulation of cytoskeleton dynamics, membrane trafficking, cell migration, and many of the metabolic responses to insulin [12,13].PtdIns(3,4,5)P3 regulates a wide variety of effector proteins primarily by binding and recruiting specific proteins.In mammalian cells, PtdIns(4,5)P2 and/or PtdIns(3,4,5)P3 are substrates for several members of the phosphoinositide 5-phosphatases family, including Inppl1 (or

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“…Figure 3 and data not shown). We also confirmed that both PtdIns(4,5)P2 and PtdIns (3,4,5)P3 are substrates for the murine Inpp5k protein (Suppl. informations and Suppl.…”

Section: Results: Production and Characterization Of Inpp5k Transgenisupporting

confidence: 77%

Section: The Inositol Inpp5k 5-phosphatase Affects Osmoregulation Thrmentioning

confidence: 99%

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

Pernot

Terryn

Cheong

et al. 2011

Pflugers Arch - Eur J Physiol

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“…PtdIns(3,5)P 2 concentrates on late compartments of the endocytic pathway, the MVB, and lysosome. PtdIns(5)P is localized in the nucleus, and generation of nuclear PtdIns(4,5)P 2 is key to regulating some aspects of gene expression (reviewed in Barlow et al 2009). Parallels can be drawn between the generation of front -rear axis in migrating cells and apical -basal polarity in polarized cell types (for recent review, see Nelson 2009).…”

Section: Small Gtpases and Phosphoinositidesmentioning

confidence: 99%

Phosphoinositides in Cell Architecture

Shewan

Eastburn²,

Mostov

2011

Cold Spring Harbor Perspectives in Biology

173

159

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Inositol phospholipids have been implicated in almost all aspects of cellular physiology including spatiotemporal regulation of cellular signaling, acquisition of cellular polarity, specification of membrane identity, cytoskeletal dynamics, and regulation of cellular adhesion, motility, and cytokinesis. In this review, we examine the critical role phosphoinositides play in these processes to execute the establishment and maintenance of cellular architecture. Epithelial tissues perform essential barrier and transport functions in almost all major organs. Key to their development and function is the establishment of epithelial cell polarity. We place a special emphasis on highlighting recent studies demonstrating phosphoinositide regulation of epithelial cell polarity and how individual cells use phosphoinositides to further organize into epithelial tissues.P hosphoinositides (PIs) are essential components of cellular membranes in eukaryotes. Though these specialized lipids comprise less than 1% of the cellular lipid cohort, they play key roles in many fundamental biological processes (Di Paolo and De Camilli 2006;Saarikangas et al. 2010). PIs possess such far ranging roles by serving as specialized membrane docking sites for effectors of numerous cellular signal transduction cascades. PIs also serve as precursors of lipid second messengers. They are concentrated on the cytosolic face of cellular membranes (Fig. 1A) and rapidly diffuse within the plane of the membrane. Reversible phosphorylation of the myo-inositol head group of phosphatidylinositol (PtdIns) at positions 3, 4, and 5 (Fig. 1B) gives rise to the seven PI isoforms identified in eukaryotic cells. PtdIns(4)P and PtdIns(4,5)P 2 are constitutively present in membranes and comprise the largest pool of cellular PIs, whereas PtdIns(3,4,5)P 3 is essentially undetectable in most types of unstimulated cells (Lemmon and Ferguson 2000;Saarikangas et al. 2010).The spatiotemporally regulated production and turnover of phosphoinositides is crucial for localized PI signaling and function. Numerous phosphatidylinositol kinases and phosphatases are involved in regulating the metabolism of the various PI isoforms (Fig. 1)

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“…These interactions facilitate PIP 2 control of diverse cellular functions. PIPKI␣ is predominantly localized to the nucleus and controls the nuclear events, whereas PIPKI␤ is targeted to perinuclear regions/endosomes (9,10). PIPKI␥ is expressed as at least six splice variants (PIPKI␥i1, PIPKI␥i2, PIPKI␥i3, PIPKI␥i4, PIPKI␥i5, and PIPKI␥i6) in mammalian cells (11,12); among them, PIPKI␥i2 can be targeted to the cell-matrix interface via an interaction with talin and plays role in focal adhesion assembly (13)(14)(15), whereas PIPKI␥i4 and PIPKI␥i5 are localized to the nucleus and endosomes, respectively (11,16).…”

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confidence: 99%

Phosphatidylinositol Phosphate 5-Kinase Iγ and Phosphoinositide 3-Kinase/Akt Signaling Couple to Promote Oncogenic Growth

Thapa

Choi

Tan

et al. 2015

Journal of Biological Chemistry

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Background: PIP 2 generated by PIPKI family members regulates many cellular functions, and PIP 2 is a PI3K substrate. Results: Loss of PIPKI␥ or PIPKI␥i2 impaired Akt activation. PIPKI␥i2 and Src activate Akt and anchorage-independent growth. Conclusion: PI3K/Akt signaling is regulated by coupling with PIPKI␥. Significance: The coupling of PIPKI␥ and PI3K indicates a mechanism for Akt activation that enhances oncogenic growth.

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Nuclear phosphoinositides: a signaling enigma wrapped in a compartmental conundrum

Cited by 124 publications

References 113 publications

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

The inositol Inpp5k 5-phosphatase affects osmoregulation through the vasopressin-aquaporin 2 pathway in the collecting system

Phosphoinositides in Cell Architecture

Phosphatidylinositol Phosphate 5-Kinase Iγ and Phosphoinositide 3-Kinase/Akt Signaling Couple to Promote Oncogenic Growth

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