The glutamic acid-rich protein-2 (GARP2) is a high affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties.

The glutamic acid-rich protein-2 is a splice variant of the beta-subunit of the cGMP-gated ion channel of rod photoreceptors. is believed to interact with several membrane-associated phototransduction proteins in rod photoreceptors. In this study, we demonstrated that Gduanyu372 is a high affinity PDE6-binding protein and that PDE6 co-purifies with Gduanyu372 during several stages of chromatographic purification. We found that hydrophobic interaction chromatography succeeds in quantitatively separating Gduanyu372 from the PDE6 holoenzyme. Furthermore, the 17-kDa prenyl-binding protein, abundant in retinal cells, selectively released PDE6 (but not from rod outer segment membranes, demonstrating the specificity of the interaction between Gduanyu372 and PDE6. Purified Gduanyu372 was able to suppress 80% of the basal activity of the nonactivated, membrane-bound PDE6 holoenzyme at concentrations equivalent to its endogenous concentration in rod outer segment membranes. However, Gduanyu372 was unable to reverse the transducin activation of PDE6 (in contrast to a previous study) nor did it significantly alter catalysis of the fully activated PDE6 catalytic dimer. The high binding affinity of Gduanyu372 for PDE6 and its ability to regulate PDE6 activity in its dark-adapted state suggest a novel role for Gduanyu372 as a regulator of spontaneous activation of rod PDE6, thereby serving to lower rod photoreceptor "dark noise" and allowing these sensory cells to operate at the single photon detection limit.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}