Role of Protein Phosphatase 2A in Regulating the Visual Signaling in<i>Drosophila</i>

Wang, Ning; Leung, Hung-Tat; Pak, William L.; Carl, Yonatan T.; Wadzinski, Brian E.; Shieh, Bih‐Hwa

doi:10.1523/jneurosci.5134-07.2008

Cited by 15 publications

(19 citation statements)

References 38 publications

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“…Indeed, we demonstrate that PP2A exhibits a concentration-dependent activity to dephosphorylate CaMKII (Fig. 3C), similar to INAD, a known substrate of PP2A (11).…”

Section: Autophosphorylation Of Camkii Is Increased By Okadaic Acid-wesupporting

confidence: 52%

“…The mts XE2258 was obtained from Bloomington Stock Center, and the ras transgene was removed (11). The ala 1 transgenic line, in which the transgene was integrated in the X-chromosome, was provided by Dr. L. Griffith (Brandeis University).…”

Section: Preparation Of Fly Head Extracts and Westernmentioning

confidence: 99%

“…To gain further insights into the role of CaMKII to modulate Arr2, and how CaMKII is reg- ulated by PP2A in vivo, we examined mts XE2258 (mts) mutants affecting the catalytic subunit of PP2A (11,42). We showed earlier that PP2A catalyzes dephosphorylation of CaMKII and is co-localized with CaMKII to regulate autophosphorylation and hence the kinase activity.…”

Section: Characterization Of Ala 1 Flies To Reveal the In Vivo Functimentioning

confidence: 99%

“…The rise of intracellular Ca 2ϩ modulates several aspects of the visual response including activation, deactivation, and light adaptation (6). For example, Ca 2ϩ together with diacylglycerol activates a classical protein kinase C, eye-PKC, which is critical for the negative regulation of visual signaling by modulating deactivation and light adaptation (7)(8)(9)(10)(11).…”

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confidence: 99%

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Role of Ca2+/Calmodulin-dependent Protein Kinase II in Drosophila Photoreceptors

Lu¹,

Leung

Wang³

et al. 2009

Journal of Biological Chemistry

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Ca2؉ modulates the visual response in both vertebrates and invertebrates. In Drosophila photoreceptors, an increase of cytoplasmic Ca 2؉ mimics light adaptation. Little is known regarding the mechanism, however. We explored the role of the sole Drosophila Ca 2؉ /calmodulin-dependent protein kinase II (CaMKII) to mediate light adaptation. CaMKII has been implicated in the phosphorylation of arrestin 2 (Arr2). However, the functional significance of Arr2 phosphorylation remains debatable. We identified retinal CaMKII by anti-CaMKII antibodies and by its Ca 2؉ -dependent autophosphorylation. Moreover, we show that phosphorylation of CaMKII is greatly enhanced by okadaic acid, and indeed, purified PP2A catalyzes the dephosphorylation of CaMKII. Significantly, we demonstrate that antiCaMKII antibodies co-immunoprecipitate, and CaMKII fusion proteins pull down the catalytic subunit of PP2A from fly extracts, indicating that PP2A interacts with CaMKII to form a protein complex. To investigate the function of CaMKII in photoreceptors, we show that suppression of CaMKII in transgenic flies affects light adaptation and increases prolonged depolarizing afterpotential amplitude, whereas a reduced PP2A activity brings about reduced prolonged depolarizing afterpotential amplitude. Taken together, we conclude that CaMKII is involved in the negative regulation of the visual response affecting light adaptation, possibly by catalyzing phosphorylation of Arr2. Moreover, the CaMKII activity appears tightly regulated by the co-localized PP2A.Visual transduction is the process that converts the signal of light (photons) into a change of membrane potential in photoreceptors (see Ref. 1 for review). Visual signaling is initiated upon the activation of rhodopsins by light: light switches on rhodopsin to generate metarhodopsin, which activates the heterotrimeric G q in Drosophila (2). Subsequently, the GTPbound G␣ q subunit activates phospholipase C␤4 encoded by the norpA (no receptor potential A) gene (3). Phospholipase C␤4 catalyzes the breakdown of phosphoinositol 4,5-bisphosphate to generate diacylglycerol, which or its metabolite has been implicated in gating the transient receptor potential (TRP) 2 and TRP-like channels (4, 5). TRP is the major Ca 2ϩ channel that mediates the light-dependent depolarization response leading to an increase of cytosolic Ca 2ϩ in photoreceptors. The rise of intracellular Ca 2ϩ modulates several aspects of the visual response including activation, deactivation, and light adaptation (6). For example, Ca 2ϩ together with diacylglycerol activates a classical protein kinase C, eye-PKC, which is critical for the negative regulation of visual signaling by modulating deactivation and light adaptation (7-11).Light adaptation is the process by which photoreceptors adjust the visual sensitivity in response to ambient background light by down-regulating rhodopsin-mediated signaling. Light adaptation can be arbitrarily subdivided into long term and short term adaptation and may involve multiple regulations to red...

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“…Indeed, we demonstrate that PP2A exhibits a concentration-dependent activity to dephosphorylate CaMKII (Fig. 3C), similar to INAD, a known substrate of PP2A (11).…”

Section: Autophosphorylation Of Camkii Is Increased By Okadaic Acid-wesupporting

confidence: 52%

Section: Preparation Of Fly Head Extracts and Westernmentioning

confidence: 99%

Section: Characterization Of Ala 1 Flies To Reveal the In Vivo Functimentioning

confidence: 99%

mentioning

confidence: 99%

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Role of Ca2+/Calmodulin-dependent Protein Kinase II in Drosophila Photoreceptors

Lu¹,

Leung

Wang³

et al. 2009

Journal of Biological Chemistry

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“…Although PP1 and PP2A are independent of divalent cations, PP2B and PP2C depend on the presence of Ca 2ϩ and Mg 2ϩ , respectively (44). PP2A, which in Drosophila is encoded by the microtubule star (mts) locus, has been shown to dephosphorylate the photoreceptor protein INAD in vitro, and a mutation in the mts gene partially rescues the phenotype of the eye-PKC deficient inaC mutant (45). In vitro studies on TRP phosphorylation and dephosphorylation using inhibitors of PP1 and PP2A, okadaic acid and microcystin, provided evidence for a possible role of these phosphatases in the dephosphorylation of TRP (19).…”

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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V‐ATPase deactivation in blowfly salivary glands is mediated by protein phosphatase 2C

Voß

Blenau

Baumann

2009

Arch Insect Biochem Physiol

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The activity of vacuolar H(+)-ATPase (V-ATPase) in the apical membrane of blowfly (Calliphora vicina) salivary glands is regulated by the neurohormone serotonin (5-HT). 5-HT induces, via protein kinase A, the phosphorylation of V-ATPase subunit C and the assembly of V-ATPase holoenzymes. The protein phosphatase responsible for the dephosphorylation of subunit C and V-ATPase inactivation is not as yet known. We show here that inhibitors of protein phosphatases PP1 and PP2A (tautomycin, ocadaic acid) and PP2B (cyclosporin A, FK-506) do not prevent V-ATPase deactivation and dephosphorylation of subunit C. A decrease in the intracellular Mg(2+) level caused by loading secretory cells with EDTA-AM leads to the activation of proton pumping in the absence of 5-HT, prolongs the 5-HT-induced response in proton pumping, and inhibits the dephosphorylation of subunit C. Thus, the deactivation of V-ATPase is most probably mediated by a protein phosphatase that is insensitive to okadaic acid and that requires Mg(2+), namely, a member of the PP2C protein family. By molecular biological techniques, we demonstrate the expression of at least two PP2C protein family members in blowfly salivary glands.

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Role of Protein Phosphatase 2A in Regulating the Visual Signaling inDrosophila

Cited by 15 publications

References 38 publications

Role of Ca2+/Calmodulin-dependent Protein Kinase II in Drosophila Photoreceptors

Role of Ca2+/Calmodulin-dependent Protein Kinase II in Drosophila Photoreceptors

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

V‐ATPase deactivation in blowfly salivary glands is mediated by protein phosphatase 2C

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