Role of protein phosphatase 2A in regulating the visual signaling in Drosophila.
Drosophila visual signaling, a G-protein-coupled phospholipase Cbeta (PLCbeta)-mediated mechanism, is regulated by eye-protein kinase C (PKC) that promotes light adaptation and fast deactivation, most likely via phosphorylation of inactivation no afterpotential D (INAD) and TRP (transient receptor potential). To reveal the critical phosphatases that dephosphorylate INAD, we used several biochemical analyses and identified protein phosphatase 2A (PP2A) as a candidate. Importantly, the catalytic subunit of PP2A, microtubule star (MTS), is copurified with INAD, and an elevated phosphorylation of INAD by eye-PKC was observed in three mts heterozygotes. To explore whether PP2A (MTS) regulates dephosphorylation of INAD by counteracting eye-PKC [INAC (inactivation no afterpotential C] in vivo, we performed ERG recordings. We discovered that inaC(P209) was semidominant, because inaC(P209) heterozygotes displayed abnormal light adaptation and slow deactivation. Interestingly, the deactivation defect of inaC(P209) heterozygotes was rescued by the mts(XE2258) heterozygous background. In contrast, mts(XE2258) failed to modify the severe deactivation of norpA(P16), indicating that MTS does not modulate NORPA (no receptor potential A) (PLCbeta). Together, our results strongly indicate that dephosphorylation of INAD is catalyzed by PP2A, and a reduction of PP2A can compensate for a partial loss of function in eye-PKC, restoring the fast deactivation kinetics in vivo. We thus propose that the fast deactivation of the visual response is modulated in part by the phosphorylation of INAD.
Wang
Ning
N
Department of Pharmacology, Center for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee 37232, USA.
Leung
Hung-Tat
HT
Pak
William L
WL
Carl
Yonatan T
YT
Wadzinski
Brian E
BE
Shieh
Bih-Hwa
BH
D000200:Action Potentials / Q000502:physiology; D000221:Adaptation, Ocular / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D005136:Eye Proteins / Q000378:metabolism / Q000502:physiology; D005260:Female; D008297:Male; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D054648:Protein Phosphatase 2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014796:Visual Perception / Q000502:physiology*
D029721:Drosophila Proteins; D005136:Eye Proteins; C091568:inaD protein, Drosophila; D054648:Protein Phosphatase 2