An Introduction to Phosphoinositides

Maffucci, Tania

doi:10.1007/978-94-007-5025-8_1

Cited by 15 publications

(37 citation statements)

References 209 publications

(317 reference statements)

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“…S4). PTEN is a phosphatase that catalyzes the conversion of PIP3 to PIP2 (26). In FCs mutant for the loss-offunction allele PTEN C494 , we again observed apically localized Pcan in distinct aggregates (Fig.…”

Section: Pip2 Levels Are a Crucial Determinant For The Polar Secretiomentioning

confidence: 56%

“…It has an indispensable role in the synthesis of phosphatidylinositol (PI) (26). Pis is required for the incorporation of an inositol group in cytidine diphosphate-diacylglycerol (CDP-DAG) to produce PI ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…2A). The phosphorylated derivatives of PI, known as PtdIns, are crucial regulators of calcium homeostasis, membrane trafficking, secretory pathways, and signal transduction (26). In particular, Pis has been shown to be essential for PIP2 regeneration after its hydrolysis by phospholipase C (PLC) (27).…”

Section: Resultsmentioning

confidence: 99%

“…Pis has been shown to be involved in PI production, and therefore in the regulation of all PtdIns levels (26). Among the various forms of PtdIns, PIP2 can mediate distinct biological activities, including cell polarity, secretion, vesicular trafficking, and cell adhesion (8)(9)(10)(11)29).…”

Section: Pip2 Levels Are a Crucial Determinant For The Polar Secretiomentioning

confidence: 99%

“…Downstream of Pis, the production of PIP2 requires two different steps, which are catalyzed by two distinct classes of PI kinases ( Fig. 2A) (26). First, PI is phosphorylated by PI4K to generate PI4P, which is then phosphorylated by PIP5K to produce PIP2.…”

Section: Pip2 Levels Are a Crucial Determinant For The Polar Secretiomentioning

confidence: 99%

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Polarized deposition of basement membrane proteins depends on Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-bisphosphate

Devergne

Tsung

Barcelo

et al. 2014

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

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The basement membrane (BM), a specialized sheet of the extracellular matrix contacting the basal side of epithelial tissues, plays an important role in the control of the polarized structure of epithelial cells. However, little is known about how BM proteins themselves achieve a polarized distribution. Here, we identify phosphatidylinositol 4,5-bisphosphate (PIP2) as a critical regulator of the polarized secretion of BM proteins. A decrease of PIP2 levels, in particular through mutations in Phosphatidylinositol synthase (Pis) and other members of the phosphoinositide pathway, leads to the aberrant accumulation of BM components at the apical side of the cell without primarily affecting the distribution of apical and basolateral polarity proteins. In addition, PIP2 controls the apical and lateral localization of Crag (Calmodulin-binding protein related to a Rab3 GDP/GTP exchange protein), a factor specifically required to prevent aberrant apical secretion of BM. We propose that PIP2, through the control of Crag's subcellular localization, restricts the secretion of BM proteins to the basal side.cell polarity | PTEN | PIK | Drosophila | oogenesis E pithelial cells are characterized by their polarized architecture, which enables them to exert their varied functions in embryonic and adult organisms. Epithelia exhibit a profound apical-basal polarity that is manifested in the cytoplasmic and surface organization of individual cells (1-3). Loss of apicalbasal cell polarity is often associated with carcinoma progression and tumor metastasis (4, 5). The establishment and maintenance of cell polarity relies on the transport of newly synthesized and recycled proteins to their correct destinations (6, 7). The lipid composition of the transport vesicles and of the plasma membrane is crucial for the establishment and maintenance of cell polarity (6-9). In particular, in 3D in vitro culture of Madin-Darby canine kidney (MDCK) cells, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), two phosphoinositides (PtdIns) have been shown to play critical roles in polarized vesicle trafficking by mediating the recruitment of proteins to these different domains (10, 11).To set up a correct cell polarity, membrane asymmetry needs to be established. In cell culture, and likely during development of many tissues in multicellular organisms, this process is achieved by two external cues: one provided by the adjacent cells via cadherin-dependent adhesion and the other by interaction with the basement membrane (BM), a specialized sheet of the ECM secreted basally by the epithelial cells (12, 13). The main components of the BM are secreted glycoproteins, such as collagen IV (Coll IV), laminin, and the heparan sulfate proteoglycan perlecan (Pcan) (14), which interact with different membrane receptors, including integrin and dystroglycan (14,15). Previous studies in model organisms and 3D culture models have shown that BM secreted by the epithelial cells at their basal side plays a role as an initial ...

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Section: Pip2 Levels Are a Crucial Determinant For The Polar Secretiomentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Pip2 Levels Are a Crucial Determinant For The Polar Secretiomentioning

confidence: 99%

Section: Pip2 Levels Are a Crucial Determinant For The Polar Secretiomentioning

confidence: 99%

See 3 more Smart Citations

Polarized deposition of basement membrane proteins depends on Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-bisphosphate

Devergne

Tsung

Barcelo

et al. 2014

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

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Qualitative and Quantitative In Vitro Analysis of Phosphatidylinositol Phosphatase Substrate Specificity

Gewinner

2016

Methods in Molecular Biology

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Phosphoinositides compromise a family of eight membrane lipids which play important roles in many cellular signaling pathways. Signaling through phosphoinositides has been shown in a variety of cellular functions such cell proliferation, cell growth, apoptosis, and vesicle trafficking. Phospholipid phosphatases regulate cell signaling by modifying the concentration of phosphoinositides and their dephosphorylated products. To understand the role of individual lipid phosphatases in phosphoinositide turnover and functional signaling, it is crucial to determine the substrate specificity of the lipid phosphatase of interest. In this chapter we describe how the substrate specificity of an individual lipid phosphatase can be qualitatively and quantitatively measured in an in vitro radiometric assay. In addition, we specify the different expression systems and purification methods required to produce the necessary yield and functionality in order to further characterize these enzymes. The outstanding versatility and sensitivity of this assay system are yet unmatched and are therefore currently considered the standard of the field.

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An Overview of Class II Phosphoinositide 3-Kinases

Heng

Maffucci

2022

Current Topics in Microbiology and Immunology

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An Introduction to Phosphoinositides

Cited by 15 publications

References 209 publications

Polarized deposition of basement membrane proteins depends on Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-bisphosphate

Polarized deposition of basement membrane proteins depends on Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-bisphosphate

Qualitative and Quantitative In Vitro Analysis of Phosphatidylinositol Phosphatase Substrate Specificity

An Overview of Class II Phosphoinositide 3-Kinases

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