Editors' ChoiceCell Biology

pH Signaling Through Arrestin

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Science Signaling  08 Jun 2010:
Vol. 3, Issue 125, pp. ec171
DOI: 10.1126/scisignal.3125ec171

Seven-transmembrane domain receptors (7TMRs), many of which are also G protein–coupled receptors, may signal through proteins other than G proteins, such as arrestins. Fungi, such as Aspergillus nidulans, signal through 7TMRs to respond to changes in pH (alkaline conditions). In A. nidulans, alkaline conditions activate a 7TMR, PalH, that is connected to an arrestin-like protein (PalF), which becomes phosphorylated and ubiquitylated. This mediates a series of protein interactions, ultimately culminating in the proteolytic activation of the pH-dependent transcription factor PacC. This pathway is normally not active under acidic conditions. Hervás-Aguilar et al. show that overexpressed PalH is not effectively delivered to the plasma membrane unless PalF is also expressed, suggesting a role for PalF in trafficking of the receptor. Expression of either of two PalF-ubiquitin fusion proteins (PalF-Ub or PalF-UbK48R) promoted PalC cleavage under acidic and neutral conditions, suggesting that ubiquitylation of PalF can bypass receptor activation by pH. Cells in which the pH signaling pathway is active exhibit sensitivity to molybdate and resistance to neomycin, and cells expressing either of the PalF-ubiquitin fusion proteins exhibited these characteristics, consistent with constitutive activation of the pathway. Whereas PalF-deficient cells failed to redistribute PacC under alkaline conditions, the presence of the PalF-ubiquitin fusion proteins promoted the recruitment of PacC to cortical structures, which are believed to be the site of its cleavage, under acidic conditions. Thus, in A. nidulans, ubiquitylated arrestin appears to be the primary mediator of the pH signal.

A. Hervás-Aguilar, A. Galindo, M. A. Peñalva, Receptor-independent ambient pH signaling by ubiquitin attachment to fungal arrestin-like PalF. J. Biol. Chem. 285, 18095–18102 (2010). [Abstract] [Full Text]

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