Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
Gene/Protein
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Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Arrestins belong to a family of multifunctional adaptor proteins that regulate internalization of diverse receptors including G-protein-coupled receptors (GPCRs). Defects associated with endocytosis of GPCRs have been linked to human diseases. We used enhanced green fluorescent protein-tagged arrestin 2 (Arr2) to monitor the turnover of the major rhodopsin (Rh1) in live Drosophila. We demonstrate that during degeneration of norpA(
P24
) photoreceptors the loss of Rh1 is parallel to the disappearance of rhabdomeres, the specialized visual organelle that houses Rh1. The cause of degeneration in norpA(
P24
) is the failure to activate
CaMKII
(Ca(2+)/calmodulin-dependent protein kinase II) and retinal degeneration C (RDGC) because of a loss of light-dependent Ca(2+) entry. A lack of activation in
CaMKII
, which phosphorylates Arr2, leads to hypophosphorylated Arr2, while a lack of activation of RDGC, which dephosphorylates Rh1, results in hyperphosphorylated Rh1. We investigated how reversible phosphorylation of Rh1 and Arr2 contributes to photoreceptor degeneration. To uncover the consequence underlying a lack of
CaMKII
activation, we characterized ala(1) flies in which
CaMKII
was suppressed by an inhibitory peptide, and showed that morphology of rhabdomeres was not affected. In contrast, we found that expression of phosphorylation-deficient Rh1s, which either lack the C terminus or contain Ala substitution in the phosphorylation sites, was able to prevent degeneration of norpA(
P24
) photoreceptors. This suppression is not due to a loss of Arr2 interaction. Importantly, co-expression of these modified Rh1s offered protective effects, which greatly delayed photoreceptor degeneration. Together, we conclude that phosphorylation of Rh1 is the major determinant that orchestrates its internalization leading to retinal degeneration.
...
PMID:Role of rhodopsin and arrestin phosphorylation in retinal degeneration of Drosophila. 2285 23
Unregulated Ca
2+
influx affects intracellular Ca
2+
homoeostasis, which may lead to neuronal death. In
Drosophila
, following the activation of rhodopsin the TRP Ca
2+
channel is open to mediate the light-dependent depolarization. A constitutively active TRP channel triggers the degeneration of
Trp
P365
/+ photoreceptors. To explore retinal degeneration, we employed a multidisciplinary approach including live imaging using GFP tagged actin and arrestin 2. Importantly, we demonstrate that the major rhodopsin (Rh1) was greatly reduced before the onset of rhabdomere degeneration; a great reduction of Rh1 affects the maintenance of rhabdomere leading to degeneration of photoreceptors.
Trp
P365
/+ also led to the up-regulation of
CaMKII
, which is beneficial as suppression of
CaMKII
accelerated retinal degeneration. We explored the regulation of TRP by investigating the genetic interaction between
Trp
P365
/+ and mutants affecting the turnover of diacylglycerol (DAG). We show a loss of phospholipase C in
norpA
P24
exhibited a great reduction of the DAG content delayed degeneration of
Trp
P365
/+ photoreceptors. In contrast, knockdown or mutations in DAG lipase (InaE) that is accompanied by slightly reduced levels of most DAG but an increased level of DAG 34:1, exacerbated retinal degeneration of
Trp
P365
/+. Together, our findings support the notion that DAG plays a role in regulating TRP. Interestingly, DAG lipase is likely required during photoreceptor development as
Trp
P365
/+;
inaE
N125
double mutants contained severely degenerated rhabdomeres.
...
PMID:Exploring Excitotoxicity and Regulation of a Constitutively Active TRP Ca
2+
Channel in Drosophila. 3320 Jun 58
