RGD Reference Report - The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye. - Rat Genome Database

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The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye.

Authors: Liu, W  Wen, W  Wei, Z  Yu, J  Ye, F  Liu, CH  Hardie, RC  Zhang, M 
Citation: Liu W, etal., Cell. 2011 Jun 24;145(7):1088-101. doi: 10.1016/j.cell.2011.05.015.
RGD ID: 11041019
Pubmed: PMID:21703451   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cell.2011.05.015   (Journal Full-text)

INAD is a scaffolding protein that regulates signaling in Drosophila photoreceptors. One of its PDZ domains, PDZ5, cycles between reduced and oxidized forms in response to light, but it is unclear how light affects its redox potential. Through biochemical and structural studies, we show that the redox potential of PDZ5 is allosterically regulated by its interaction with another INAD domain, PDZ4. Whereas isolated PDZ5 is stable in the oxidized state, formation of a PDZ45 "supramodule" locks PDZ5 in the reduced state by raising the redox potential of its Cys606/Cys645 disulfide bond by approximately 330 mV. Acidification, potentially mediated via light and PLCbeta-mediated hydrolysis of PIP(2), disrupts the interaction between PDZ4 and PDZ5, leading to PDZ5 oxidation and dissociation from the TRP Ca(2+) channel, a key component of fly visual signaling. These results show that scaffolding proteins can actively modulate the intrinsic redox potentials of their disulfide bonds to exert regulatory roles in signaling.



Objects referenced in this article
Gene Apba1 amyloid beta precursor protein binding family A member 1 Rattus norvegicus
Gene Cspg4 chondroitin sulfate proteoglycan 4 Rattus norvegicus
Gene F11r F11 receptor Rattus norvegicus
Gene Nrxn1 neurexin 1 Rattus norvegicus

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