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Neuroscience ; 396: 66-72, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30458219

RESUMO

Drosophila phototransduction occurs in light-sensitive microvilli arranged in a longitudinal structure of the photoreceptor, termed the rhabdomere. Rhodopsin (Rh), isomerized by light, couples to G-protein, which activates phospholipase C (PLC), which in turn cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) generating diacylglycerol (DAG), inositol trisphosphate and H+. This pathway opens the light-dependent channels, transient receptor potential (TRP) and transient receptor potential like (TRPL). PLC and TRP are held together in a protein assembly by the scaffold protein INAD. We report that the channels can be photoactivated in on-cell rhabdomeric patches and in excised patches by DAG. In excised patches, addition of PLC-activator, m-3M3FBS, or G-protein-activator, GTP-γ-S, opened TRP. These reagents were ineffective in PLC-mutant norpA and in the presence of PLC inhibitor U17322. However, DAG activated TRP even when PLC was pharmacologically or mutationally suppressed. These observations indicate that PLC, G-protein, and TRP were retained functional in these patches. DAG also activated TRP in the protein kinase C (PKC) mutant, inaC, excluding the possibility that PKC could mediate DAG-dependent TRP activation. Labeling diacylglycerol kinase (DGK) by fusion of fluorescent mCherry (mCherry-DGK) indicates that DGK, which returns DAG to dark levels, is highly expressed in the microvilli. In excised patches, TRP channels could be light-activated in the presence of GTP, which is required for G-protein activation. The evidence indicates that the proteins necessary for phototransduction are retained functionally after excision and that DAG is necessary and sufficient for TRP opening. This work opens up unique possibilities for studying, in sub-microscopic native membrane patches, the ubiquitous phosphoinositide signaling pathway and its regulatory mechanisms in unprecedented detail.


Assuntos
Ativação do Canal Iônico/efeitos da radiação , Luz , Microvilosidades/metabolismo , Microvilosidades/efeitos da radiação , Células Fotorreceptoras de Invertebrados/citologia , Canais de Potencial de Receptor Transitório/metabolismo , Canais de Potencial de Receptor Transitório/efeitos da radiação , Animais , Diacilglicerol Quinase/biossíntese , Diglicerídeos/farmacologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/isolamento & purificação , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/efeitos da radiação , Drosophila melanogaster , Guanosina 5'-O-(3-Tiotrifosfato)/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Proteína Quinase C/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sulfonamidas/farmacologia , Canais de Potencial de Receptor Transitório/isolamento & purificação , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/genética
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