Retinophilin Is a Light-Regulated Phosphoprotein Required to Suppress Photoreceptor Dark Noise in Drosophila

Mecklenburg, Kirk L.; Takemori, Nobuaki; Komori, Naoka; Chu, Brian; Hardie, Roger C.; Matsumoto, Hiroyuki; O'Tousa, Joseph E.

doi:10.1523/jneurosci.4464-09.2010

Cited by 26 publications

(40 citation statements)

References 54 publications

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“…From this collection we identified the MORN family member retinophilin ( rtp , also called undertaker ( uta )). Retinophilin participates in termination of phototransduction in the fly retina (Mecklenburg et al, 2010; Venkatachalam et al, 2010) and in store-operated calcium release and phagocytosis in fly embryonic macrophages (Cuttell et al, 2008). It contains four MORN repeats, regions that can bind to phospholipid membranes (Ma et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

“…The RNAi protection is quantitatively modest, but consistent (Figure 5B). To test whether loss of Retinophilin is responsible for this phenotype, we generated a transheterozygote between two previously characterized loss-of-function mutant alleles of rtp (Mecklenburg et al, 2010; Venkatachalam et al, 2010). Axons in this rtp mutant are preserved following taxol treatment (Figure 5C and D), confirming that removal of retinophilin is indeed axoprotective.…”

Section: Resultsmentioning

confidence: 99%

“…The following strains were used in this study: Canton S (wild type), elav-GAL4 (Yao and White, 1994), pickpocket 5 -EGFP (referred to as ppkEGFP , Grueber et al, 2003), pickpocket-CD8:3xGFP (referred to as ppkCD8GFP , Shimono et al, 2009), ppk-GAL4 (Grueber et al, 2007), wnd 2 and wnd 3 mutant alleles (Collins et al, 2006), UAS-dmNMNAT (MacDonald et al, 2006), retin 1 (Venkatachalam et al, 2010), and rtp 1 (Mecklenburg et al, 2010). All other strains are from the Bloomington Stock Center.…”

Section: Methodsmentioning

confidence: 99%

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A Model of Toxic Neuropathy inDrosophilaReveals a Role for MORN4 in Promoting Axonal Degeneration

Bhattacharya

Gerdts²,

Naylor³

et al. 2012

J. Neurosci.

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Axonal degeneration is a molecular self-destruction cascade initiated following traumatic, toxic, and metabolic insults. Its mechanism underlies a number of disorders including hereditary and diabetic neuropathies and the neurotoxic side effects of chemotherapy drugs. Molecules that promote axonal degeneration could represent potential targets for therapy. To identify such molecules, we designed a screening platform based on intoxication of Drosophila larvae with paclitaxel (taxol), a chemotherapeutic agent that causes neuropathy in cancer patients. In Drosophila, taxol treatment causes swelling, fragmentation, and loss of axons in larval peripheral nerves. This axonal loss is not due to apoptosis of neurons. Taxol-induced axonal degeneration in Drosophila shares molecular execution mechanisms with vertebrates, including inhibition by both NMNAT expression and loss of wallenda/DLK. In a pilot RNAi-based screen we found that knockdown of retinophilin (rtp), which encodes a MORN-repeat containing protein, protects axons from degeneration in the presence of taxol. Loss-of-function mutants of rtp replicate this axonal protection. Knockdown of rtp also delays axonal degeneration in severed olfactory axons. We demonstrate that the mouse ortholog of rtp, MORN4, promotes axonal degeneration in mouse sensory axons following axotomy, illustrating conservation of function. Hence, this new model can identify evolutionarily conserved genes that promote axonal degeneration, and so could identify candidate therapeutic targets for a wide-range of axonopathies.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A Model of Toxic Neuropathy inDrosophilaReveals a Role for MORN4 in Promoting Axonal Degeneration

Bhattacharya

Gerdts²,

Naylor³

et al. 2012

J. Neurosci.

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“…Rhodopsin and the regulatory protein arrestin2 that binds to rhodopsin and thereby inactivates the receptor quickly become phosphorylated when the eyes are illuminated (46 -49). The recently characterized phosphoprotein retinophilin, which is required to suppress photoreceptor dark noise, becomes dephosphorylated when the flies are kept in the light (50). Another example for light-dependent dephosphorylation is Drosophila dMoesin (51).…”

Section: Discussionmentioning

confidence: 99%

Light-dependent Phosphorylation of the Drosophila Transient Receptor Potential Ion Channel

Voolstra

Beck

Oberegelsbacher

et al. 2010

Journal of Biological Chemistry

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Reversible protein phosphorylation is a well established mechanism for regulating the activity of ion channels. Typically, the pattern of phosphorylation of ion channels is complex, involving several phosphorylation sites with consensus sequences for a number of protein kinases, such as protein kinase C (PKC), 3 protein kinase A, calcium/calmodulin-dependent protein kinase, or casein kinase, which phosphorylate serine and threonine residues, as well as kinases phosphorylating tyrosine residues. For example, in the major delayed rectifier K ϩ channel Kv2.1, expressed in most central neurons, 16 phosphorylation sites have been identified by mass spectrometry, a subset of which contributes to graded modulation of voltagedependent gating (2).Transient receptor potential (TRP) channels constitute a protein family of about 30 unique homologs that are assigned to seven subfamilies on the basis of sequence homology: canonical TRPC, vanilloid TRPV, melastatin TRPM, polycystin TRPP, mucolipin TRPML, and ankyrin transmembrane proteins TRPA and NOMPC-like TRPN (3, 4). The founding member of this protein family is the Drosophila TRP channel, which, together with its homolog TRP-like (TRPL), is located in the rhabdomeral photoreceptor membrane of the fly compound eye and represents the major light-sensitive ion channel in this phospholipase C-mediated visual transduction cascade (5). Phosphorylation of several TRP channels has been described. Among the vertebrate TRPC channels, TRPC3 and TRPC6 are inhibited by phosphorylation events mediated by protein kinase C and protein kinase G (6 -8). In contrast, Src kinase activity is required for the activation of TRPC3 by diacylglycerol (9), and Fyn kinase phosphorylates and thereby increases the activity of TRPC6 (10). Abolition of the putative protein kinase C phosphorylation site Thr 635 in the S4/S5 linker region of TRPC3 by mutation results in increased channel activity and was found to underlie the phenotype of moonwalker mice, which is caused by loss of Purkinje cells (11). The regulation of the capsaicin-and heat-sensitive TRPV1 channel through phosphorylation of serine residues by protein kinase C is also well established (12)(13)(14). Phosphorylation of TRPV1 sensitizes this channel to capsaicin, heat, and other agonists. Besides protein kinase C, calcium/calmodulin-dependent kinase and protein kinase A were implicated in phosphorylation of TRPV1 (15, 16).The first TRP channel shown to become phosphorylated again was the Drosophila TRP channel. This channel is part of a signaling complex assembled by the INAD scaffold protein together with phospholipase C and an eye-enriched protein kinase C (eye-PKC) encoded by the inaC gene. It was shown initially for the larger fly Calliphora vicina and later also for Drosophila that the addition of ATP to the isolated signaling complex resulted in phosphorylation of TRP and INAD, suggesting that these two proteins of the signaling complex are targets of the associated protein kinase C (17)(18)(19)

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“…aegypti noted apparent dramatic diel changes in rhabdom volume (88). These changes might be driven by the circadian system through both NINAC and RTP, which are both required for normal rhabdomere volume in Drosophila (87,89). Many of these visual system genes continue to be rhythmic in DD conditions, suggesting that components of visual transduction are under circadian clock control (Fig.…”

mentioning

confidence: 98%

Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae

Rund

Hou

Ward

et al. 2011

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

174

269

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Anopheles gambiae, the primary African vector of malaria parasites, exhibits numerous rhythmic behaviors including flight activity, swarming, mating, host seeking, egg laying, and sugar feeding. However, little work has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is regulated globally by diel and circadian mechanisms, we have undertaken a DNA microarray analysis of An. gambiae under light/ dark cycle (LD) and constant dark (DD) conditions. Adult mated, non-blood-fed female mosquitoes were collected every 4 h for 48 h, and samples were processed with DNA microarrays. Using a cosine wave-fitting algorithm, we identified 1,293 and 600 rhythmic genes with a period length of 20-28 h in the head and body, respectively, under LD conditions, representing 9.7 and 4.5% of the An. gambiae gene set. A majority of these genes was specific to heads or bodies. Examination of mosquitoes under DD conditions revealed that rhythmic programming of the transcriptome is dependent on an interaction between the endogenous clock and extrinsic regulation by the LD cycle. A subset of genes, including the canonical clock components, was expressed rhythmically under both environmental conditions. A majority of genes had peak expression clustered around the day/night transitions, anticipating dawn and dusk. Genes cover diverse biological processes such as transcription/translation, metabolism, detoxification, olfaction, vision, cuticle regulation, and immunity, and include rate-limiting steps in the pathways. This study highlights the fundamental roles that both the circadian clock and light play in the physiology of this important insect vector and suggests targets for intervention.

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Retinophilin Is a Light-Regulated Phosphoprotein Required to Suppress Photoreceptor Dark Noise in Drosophila

Cited by 26 publications

References 54 publications

A Model of Toxic Neuropathy inDrosophilaReveals a Role for MORN4 in Promoting Axonal Degeneration

A Model of Toxic Neuropathy inDrosophilaReveals a Role for MORN4 in Promoting Axonal Degeneration

Light-dependent Phosphorylation of the Drosophila Transient Receptor Potential Ion Channel

Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae

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