Phosphoinositide Lipids in Ocular Tissues

Rajala, Ammaji; McCauley, Austin; Brush, Richard S.; Nguyen, Khuong B.; Rajala, Raju V S

doi:10.3390/biology9060125

Cited by 7 publications

(5 citation statements)

References 52 publications

(98 reference statements)

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“…The myo -inositol concentration was determined as described previously [ 48 ]. The phosphoinositide extraction and the levels of PI(3)P, PI(4)P, PI(3,4)P 2 , PI(4,5)P 2, and PI(3,4,5)P 3 were determined as described previously [ 49 ]. Lipid phosphorous was determined as described and we normalized the phosphoinositide levels to phospholipid [ 49 ].…”

Section: Methodsmentioning

confidence: 99%

Insulin-like growth factor 1 receptor mediates photoreceptor neuroprotection

et al. 2022

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Insulin-like growth factor I (IGF-1) is a neurotrophic factor and is the ligand for insulin-like growth factor 1 receptor (IGF-1R). Reduced expression of IGF-1 has been reported to cause deafness, mental retardation, postnatal growth failure, and microcephaly. IGF-1R is expressed in the retina and photoreceptor neurons; however, its functional role is not known. Global IGF-1 KO mice have age-related vision loss. We determined that conditional deletion of IGF-1R in photoreceptors and pan-retinal cells produces age-related visual function loss and retinal degeneration. Retinal pigment epithelial cell-secreted IGF-1 may be a source for IGF-1R activation in the retina. Altered retinal, fatty acid, and phosphoinositide metabolism are observed in photoreceptor and retinal cells lacking IGF-1R. Our results suggest that the IGF-1R pathway is indispensable for photoreceptor survival, and activation of IGF-1R may be an essential element of photoreceptor and retinal neuroprotection.

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Section: Methodsmentioning

confidence: 99%

Insulin-like growth factor 1 receptor mediates photoreceptor neuroprotection

et al. 2022

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“…The phosphoinositide-binding proteins are coupled to enzymes, peroxidase-conjugated antibodies, or antibody epitopes for the detection and quantification of various PIPs in cells and tissues ( 53 , 309 , 310 ). In photoreceptor cells, PI3K-generated products have been shown using phosphoinositide-binding proteins coupled with rhodopsin 1D4 antibody epitope on ELISA ( 53 , 311 ). Fluorescence resonance energy transfer is another technique to determine the binding between PIP and phosphoinositide-binding proteins ( 3 ).…”

Section: Methods To Detect Cellular Levels Of Phosphoinositidesmentioning

confidence: 99%

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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“…Mouse retinas were homogenized in phosphate-buffered saline (PBS) and the retinal phosphoinositides were extracted as described [ 13 ]. Lipid phosphorous was measured according to the method described [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

“…Lipid phosphorous was measured according to the method described [ 14 ]. Phosphoinositide lipids PI(3)P, PI(4)P, PI(3,4)P 2 , PI(4,5)P 2 , and PI(3,4,5)P 3 were measured by ELISA using PIP-binding protein probes [ 13 ]. The obtained luminescence was normalized to phospholipid [ 15 ], calculated by measuring lipid phosphorous [ 14 ] in the extracted phosphoinositide fraction from the respective retina.…”

Section: Methodsmentioning

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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Phosphoinositide Lipids in Ocular Tissues

Cited by 7 publications

References 52 publications

Insulin-like growth factor 1 receptor mediates photoreceptor neuroprotection

Insulin-like growth factor 1 receptor mediates photoreceptor neuroprotection

Signaling roles of phosphoinositides in the retina

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

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