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Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.

LaLonde MM, Janssens H, Rosenbaum E, Choi SY, Gergen JP, Colley NJ, Stark WS, Frohman MA - J. Cell Biol. (2005)

Bottom Line: Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined.We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process.Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular and Cellular Biology, Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794, USA.

ABSTRACT
Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined. We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process. Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration. Pld overexpression rescues flies lacking PLC from light-induced, metarhodopsin-mediated degeneration and restores visual signaling in flies lacking the PI transfer protein, which is a key player in the replenishment of the PI 4,5-bisphosphate (PIP2) substrate used by PLC to transduce light stimuli into neurological signals. Altogether, these findings suggest that Pld facilitates phototransduction by maintaining adequate levels of PIP2 and by protecting the visual system from metarhodopsin-induced, low light degeneration.

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Phototransduction model. TRP channel activation not only leads to the depolarization of the photoreceptor cell, but it also facilitates the conversion of activated metarhodopsin to inactive rhodopsin via the phosphorylation of Ca2+/CaM kinase, which in turn phosphorylates arrestin2 (Arr2) and causes its dissociation from metarhodopsin (Introduction). Gene names are indicated in italics, phospholipids in bold, and proteins are circled; the circled numbers indicate potential sites of action for Pld as described in the text (see Introduction).
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fig1: Phototransduction model. TRP channel activation not only leads to the depolarization of the photoreceptor cell, but it also facilitates the conversion of activated metarhodopsin to inactive rhodopsin via the phosphorylation of Ca2+/CaM kinase, which in turn phosphorylates arrestin2 (Arr2) and causes its dissociation from metarhodopsin (Introduction). Gene names are indicated in italics, phospholipids in bold, and proteins are circled; the circled numbers indicate potential sites of action for Pld as described in the text (see Introduction).

Mentions: The phototransduction cycle of Drosophila melanogaster is one of the best understood examples of inositol lipid signaling. As in most invertebrates, phototransduction in D. melanogaster uses a G protein–coupled phosphoinositide pathway (Fig. 1; for reviews see Montell, 1999; Hardie, 2001; Hardie and Raghu, 2001) wherein photoisomerization of rhodopsin to metarhodopsin in the photoreceptor rhabdomeric microvilli activates heterotrimeric Gq. Gq-α then activates a phosphatidylinositol (PI)-specific PLC, which hydrolyzes PI 4,5-bisphosphate (PIP2), generating inositol 1,4,5-triphosphate (IP3) and DAG. Direct action of IP3 on endoplasmic reticulum calcium stores and the stimulation of protein kinase C by DAG are not thought to underlie the subsequent Ca+ surge that triggers depolarization because genetic inactivation of either the single IP3 receptor or the single protein kinase C isoform does not eliminate phototransduction (Raghu et al., 2000a). Instead, through some other mechanism (Raghu et al., 2000b), DAG mediates the opening of several classes of light-sensitive cation channels: transient receptor potential (TRP; Montell and Rubin, 1989; Hardie and Minke, 1992), TRP-like (Phillips et al., 1992; Niemeyer et al., 1996; Xu et al., 2000), and TRP-γ (Xu et al., 2000). It has been proposed that conversion of DAG into polyunsaturated fatty acids mediates TRP activation (Chyb et al., 1999; Raghu et al., 2000b), but this remains controversial as DAG lipase activity has not yet been demonstrated in D. melanogaster (Agam et al., 2000, 2004; O'Tousa, 2002).


Regulation of phototransduction responsiveness and retinal degeneration by a phospholipase D-generated signaling lipid.

LaLonde MM, Janssens H, Rosenbaum E, Choi SY, Gergen JP, Colley NJ, Stark WS, Frohman MA - J. Cell Biol. (2005)

Phototransduction model. TRP channel activation not only leads to the depolarization of the photoreceptor cell, but it also facilitates the conversion of activated metarhodopsin to inactive rhodopsin via the phosphorylation of Ca2+/CaM kinase, which in turn phosphorylates arrestin2 (Arr2) and causes its dissociation from metarhodopsin (Introduction). Gene names are indicated in italics, phospholipids in bold, and proteins are circled; the circled numbers indicate potential sites of action for Pld as described in the text (see Introduction).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171926&req=5

fig1: Phototransduction model. TRP channel activation not only leads to the depolarization of the photoreceptor cell, but it also facilitates the conversion of activated metarhodopsin to inactive rhodopsin via the phosphorylation of Ca2+/CaM kinase, which in turn phosphorylates arrestin2 (Arr2) and causes its dissociation from metarhodopsin (Introduction). Gene names are indicated in italics, phospholipids in bold, and proteins are circled; the circled numbers indicate potential sites of action for Pld as described in the text (see Introduction).
Mentions: The phototransduction cycle of Drosophila melanogaster is one of the best understood examples of inositol lipid signaling. As in most invertebrates, phototransduction in D. melanogaster uses a G protein–coupled phosphoinositide pathway (Fig. 1; for reviews see Montell, 1999; Hardie, 2001; Hardie and Raghu, 2001) wherein photoisomerization of rhodopsin to metarhodopsin in the photoreceptor rhabdomeric microvilli activates heterotrimeric Gq. Gq-α then activates a phosphatidylinositol (PI)-specific PLC, which hydrolyzes PI 4,5-bisphosphate (PIP2), generating inositol 1,4,5-triphosphate (IP3) and DAG. Direct action of IP3 on endoplasmic reticulum calcium stores and the stimulation of protein kinase C by DAG are not thought to underlie the subsequent Ca+ surge that triggers depolarization because genetic inactivation of either the single IP3 receptor or the single protein kinase C isoform does not eliminate phototransduction (Raghu et al., 2000a). Instead, through some other mechanism (Raghu et al., 2000b), DAG mediates the opening of several classes of light-sensitive cation channels: transient receptor potential (TRP; Montell and Rubin, 1989; Hardie and Minke, 1992), TRP-like (Phillips et al., 1992; Niemeyer et al., 1996; Xu et al., 2000), and TRP-γ (Xu et al., 2000). It has been proposed that conversion of DAG into polyunsaturated fatty acids mediates TRP activation (Chyb et al., 1999; Raghu et al., 2000b), but this remains controversial as DAG lipase activity has not yet been demonstrated in D. melanogaster (Agam et al., 2000, 2004; O'Tousa, 2002).

Bottom Line: Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined.We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process.Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular and Cellular Biology, Center for Developmental Genetics, Stony Brook University, Stony Brook, NY 11794, USA.

ABSTRACT
Drosophila melanogaster phototransduction proceeds via a phospholipase C (PLC)-triggered cascade of phosphatidylinositol (PI) lipid modifications, many steps of which remain undefined. We describe the involvement of the lipid phosphatidic acid and the enzyme that generates it, phospholipase D (Pld), in this process. Pld() flies exhibit decreased light sensitivity as well as a heightened susceptibility to retinal degeneration. Pld overexpression rescues flies lacking PLC from light-induced, metarhodopsin-mediated degeneration and restores visual signaling in flies lacking the PI transfer protein, which is a key player in the replenishment of the PI 4,5-bisphosphate (PIP2) substrate used by PLC to transduce light stimuli into neurological signals. Altogether, these findings suggest that Pld facilitates phototransduction by maintaining adequate levels of PIP2 and by protecting the visual system from metarhodopsin-induced, low light degeneration.

Show MeSH
Related in: MedlinePlus