Phosphoinositides: Minor Lipids Make a Major Impact on Photoreceptor Cell Functions

Rajala, Raju V S; Rajala, Ammaji; Morris, Andrew J.; Anderson, Robert E.

doi:10.1038/srep05463

Cited by 8 publications

(7 citation statements)

References 36 publications

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“…DHA is highly abundant in retinal layers and is the major PUFA component (up to 60%) . The major tissue phosphatidyl inositol PI(38:4) m/z 885.5497 was found predominantly confined to the photoreceptor cell layer (inner and outer segments), consistent with the functional role of PIs in rod outer segments, and at lower abundances throughout other tissues types (Figure E). The ganglioside, GM1(38:1) m/z 1572.9090, was detected at low abundance and localised in the inner retinal layers (nerve fibre layer and ganglion cell layer) and optic nerve bundle, consistent with its previous detection in mammalian retinae …”

Section: Resultssupporting

confidence: 60%

Detection of small molecule concentration gradients in ocular tissues and humours

et al. 2019

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The eye is an elegant organ consisting of a number of tissues and fluids with specialised functions that together allow it to effectively transmit and transduce light input to the brain for visual perception. One key determinant of this integrated function is the spatial relationship of ocular tissues. Biomolecular distributions within the main ocular tissues cornea, lens, and retina have been studied extensively in isolation, yet the potential for metabolic communication between ocular tissues via the ocular humours has been difficult to visualise. To address this limitation, the current study presents a method to map spatial distributions of metabolites and small molecules in whole eyes, including ocular humours. Using a tape-transfer system and freeze-drying, the spatial distribution of ocular small molecules was investigated in mouse, rat, fish (black bream), and rabbit eyes using negative ion mode MALDI imaging mass spectrometry. Full-scan imaging was used for discovery experiments, while MS/MS imaging for identification and localisation was also demonstrated. In all eyes, metabolites such as glutathione and phospholipids were localised in the main ocular tissues. In addition, in rodent eyes, major metabolites were distributed relatively uniformly in ocular humours.In contrast, both uniform and spatially defined ocular metabolite distributions were observed in the black bream eye. Tissue and ocular humour distributions were reproducible, as demonstrated by the three-dimensional analysis of a mouse eye, and able to be captured with high spatial resolution analysis. The presented method could be used to further investigate the role of inter-tissue metabolism in ocular health, and to support the development of therapeutics to treat major ocular diseases.

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Section: Resultssupporting

confidence: 60%

Detection of small molecule concentration gradients in ocular tissues and humours

et al. 2019

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“…The lipid substrate phosphatidylinositol (PI) serves as a substrate for PI3K to form PI-3-P [24]. PI-3-P antibody was used to stain retinal sections from dark- and light-adapted Nrl −/− mice.…”

Section: Resultsmentioning

confidence: 99%

Activation of oncogenic tyrosine kinase signaling promotes insulin receptor-mediated cone photoreceptor survival

2016

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In humans, daylight vision is primarily mediated by cone photoreceptors. These cells die in age-related retinal degenerations. Prolonging the life of cones for even one decade would have an enormous beneficial effect on usable vision in an aging population. Photoreceptors are postmitotic, but shed 10% of their outer segments daily, and must synthesize the membrane and protein equivalent of a proliferating cell each day. Although activation of oncogenic tyrosine kinase and inhibition of tyrosine phosphatase signaling is known to be essential for tumor progression, the cellular regulation of this signaling in postmitotic photoreceptor cells has not been studied. In the present study, we report that a novel G-protein coupled receptor–mediated insulin receptor (IR) signaling pathway is regulated by non-receptor tyrosine kinase Src through the inhibition of protein tyrosine phosphatase IB (PTP1B). We demonstrated the functional significance of this pathway through conditional deletion of IR and PTP1B in cones, in addition to delaying the death of cones in a mouse model of cone degeneration by activating the Src. This is the first study demonstrating the molecular mechanism of a novel signaling pathway in photoreceptor cells, which provides a window of opportunity to save the dying cones in retinal degenerative diseases.

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“…This was accomplished by delivering constructs encoding GFP sensors of PI(4,5)P 2 and PI(4)P into mouse rods by in vivo electroporation. Previous studies had reported light-dependent changes in the levels of these phosphoinositides [ 33 ] and their modulatory effects on the phototransduction cascade [ 34 ] and enzymatic activities (also reviewed in [ 16 , 17 , 35 , 36 ]). Therefore, we designed experiments allowing us to assess the presence of phosphoinositides in different subcellular compartments of the rod cells, particularly the light-sensitive outer segment.…”

Section: Resultsmentioning

confidence: 99%

Phosphoinositide Profile of the Mouse Retina

Finkelstein

Gospe

Schuhmann

et al. 2020

Cells

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Phosphoinositides are known to play multiple roles in eukaryotic cells. Although dysregulation of phosphoinositide metabolism in the retina has been reported to cause visual dysfunction in animal models and human patients, our understanding of the phosphoinositide composition of the retina is limited. Here, we report a characterization of the phosphoinositide profile of the mouse retina and an analysis of the subcellular localization of major phosphorylated phosphoinositide forms in light-sensitive photoreceptor neurons. Using chromatography of deacylated phosphatidylinositol headgroups, we established PI(4,5)P2 and PI(4)P as two major phosphorylated phosphoinositides in the retina. Using high-resolution mass spectrometry, we revealed 18:0/20:4 and 16:0/20:4 as major fatty-acyl chains of retinal phosphoinositides. Finally, analysis of fluorescent phosphoinositide sensors in rod photoreceptors demonstrated distinct subcellular distribution patterns of major phosphoinositides. The PI(4,5)P2 reporter was enriched in the inner segments and synapses, but was barely detected in the light-sensitive outer segments. The PI(4)P reporter was mostly found in the outer and inner segments and the areas around nuclei, but to a lesser degree in the synaptic region. These findings provide support for future mechanistic studies defining the biological significance of major mono- (PI(4)P) and bisphosphate (PI(4,5)P2) phosphatidylinositols in photoreceptor biology and retinal health.

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Phosphoinositides: Minor Lipids Make a Major Impact on Photoreceptor Cell Functions

Cited by 8 publications

References 36 publications

Detection of small molecule concentration gradients in ocular tissues and humours

Detection of small molecule concentration gradients in ocular tissues and humours

Activation of oncogenic tyrosine kinase signaling promotes insulin receptor-mediated cone photoreceptor survival

Phosphoinositide Profile of the Mouse Retina

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