Multiple phosphatidylinositol(3)phosphate roles in retinal pigment epithelium membrane recycling

He, Feng; Ma, Agosto; Rm, Nichols; Wensel, Theodore G.

doi:10.1101/2020.01.09.899815

Cited by 7 publications

(7 citation statements)

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“…In the retina, there is an active PIP cycle that responds to light [ 12 , 34 ]. Both class I PI3K and class III P3K signaling pathways are essential for cone photoreceptor function and survival [ 32 , 35 ], whereas class III P3K is essential for rod photoreceptor [ 36 ], rod bipolar [ 37 ], and retinal pigment epithelium cell functions [ 38 ]. In the retina, PIPs play an important role in channel modulation, phototransduction, vesicular transport, ciliogenesis, and cell survival [ 12 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Phosphoinositide Levels in the Retina by Protein Tyrosine Phosphatase 1B and Growth Factor Receptor-Bound Protein 14

et al. 2021

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Protein tyrosine kinases and protein phosphatases play a critical role in cellular regulation. The length of a cellular response depends on the interplay between activating protein kinases and deactivating protein phosphatases. Protein tyrosine phosphatase 1B (PTP1B) and growth factor receptor-bound protein 14 (Grb14) are negative regulators of receptor tyrosine kinases. However, in the retina, we have previously shown that PTP1B inactivates insulin receptor signaling, whereas phosphorylated Grb14 inhibits PTP1B activity. In silico docking of phosphorylated Grb14 and PTP1B indicate critical residues in PTP1B that may mediate the interaction. Phosphoinositides (PIPs) are acidic lipids and minor constituents in the cell that play an important role in cellular processes. Their levels are regulated by growth factor signaling. Using phosphoinositide binding protein probes, we observed increased levels of PI(3)P, PI(4)P, PI(3,4)P2, PI(4,5)P2, and PI(3,4,5)P3 in PTP1B knockout mouse retina and decreased levels of these PIPs in Grb14 knockout mouse retina. These observations suggest that the interplay between PTP1B and Grb14 can regulate PIP metabolism.

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Section: Discussionmentioning

confidence: 99%

Regulation of Phosphoinositide Levels in the Retina by Protein Tyrosine Phosphatase 1B and Growth Factor Receptor-Bound Protein 14

et al. 2021

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“…Fluorescently tagged phosphoinositide-binding protein (either GFP or DsRed) or antibodies against fusion proteins have been used as probes for the immunoelectron or fluorescent microscopic detection of specific localization of PIPs ( 302 ). In rod photoreceptor cells, RPE cells, zebrafish, and transgenic Xenopus retina, PIP probes have been successfully employed to determine the localization of specific PIPs ( 53 , 66 , 100 , 217 , 218 ).…”

Section: Methods To Detect Cellular Levels Of Phosphoinositidesmentioning

confidence: 99%

“…Some studies show that PI(3)P regulates immune cell function and phagocytosis ( 97 , 98 ). Class III PI3K plays an important role in rod, bipolar, and RPE cell functions in the retina ( 14 , 53 , 99 , 100 ).…”

Section: Phosphoinositide 3-kinasesmentioning

confidence: 99%

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Signaling roles of phosphoinositides in the retina

Rajala

2021

Journal of Lipid Research

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The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (PIs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of PI kinases and PI phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule phosphatidylinositol. PI signals regulate a wide range of cellular functions, including cytoskeletal assembly, membrane binding and fusion, ciliogenesis, vesicular transport, and signal transduction. Given the many excellent reviews on phosphoinositide kinases, phosphoinositide phosphatases, and PIs in general, in this review, we discuss recent studies and advances in PI lipid signaling in the retina. We specifically focus on PI lipids from vertebrate (e.g. bovine, rat, mice, toad, and zebrafish) and invertebrate (e.g. drosophila, horseshoe crab, and squid) retinas. We also discuss the importance of PIs revealed from animal models and human diseases, and methods to study PI levels both in vitro and in vivo. We propose that future studies should investigate the function and mechanism of activation of PI-modifying enzymes/phosphatases and further unravel PI regulation and function in the different cell types of the retina.

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“…In the retina, the PI signaling pathway is light-dependent, and most of the enzymes of the PI cycle are activated by light [6][7][8][9]. The PI levels in rod outer segments and the role of PI(3)P in rods, bipolar cells, and RPE have been reported [6,[10][11][12][13]. Earlier studies showed that During viral infection, pathogens hijack the PI pathways and use them for entry and survival in the host cell [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Phosphoinositide Lipids in Ocular Tissues

Rajala

McCauley

Brush

et al. 2020

Biology

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Inositol phospholipids play an important role in cell physiology. The inositol head groups are reversibly phosphorylated to produce seven distinct phosphorylated inositides, commonly referred to as phosphoinositides (PIs). These seven PIs are dynamically interconverted from one PI to another by the action of PI kinases and PI phosphatases. The PI signals regulate a wide variety of cellular functions, including organelle distinction, vesicular transport, cytoskeletal organization, nuclear events, regulation of ion channels, cell signaling, and host–pathogen interactions. Most of the studies of PIs in ocular tissues are based on the PI enzymes and PI phosphatases. In this study, we examined the PI levels in the cornea, retinal pigment epithelium (RPE), and retina using PI-binding protein as probes. We have examined the lipids PI(3)P, PI(4)P, PI(3,4)P2, PI(4,5)P2, and PI(3,4,5)P3, and each is present in the cornea, RPE, and retina. Alterations in the levels of these PIs in mouse models of retinal disease and corneal infections have been reported, and the results of our study will help in the management of anomalous phosphoinositide metabolism in ocular tissues.

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Multiple phosphatidylinositol(3)phosphate roles in retinal pigment epithelium membrane recycling

Cited by 7 publications

References 96 publications

Regulation of Phosphoinositide Levels in the Retina by Protein Tyrosine Phosphatase 1B and Growth Factor Receptor-Bound Protein 14

Regulation of Phosphoinositide Levels in the Retina by Protein Tyrosine Phosphatase 1B and Growth Factor Receptor-Bound Protein 14

Signaling roles of phosphoinositides in the retina

Phosphoinositide Lipids in Ocular Tissues

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