Sci. STKE, 7 February 2006
VISION Calcium Turns a Blind Eye to an Unchaperoned Photoreceptor
Rosenbaum et al. have uncovered an intriguing duality of function for calnexin, a calcium-binding molecular chaperone with an N-terminal domain in the lumen of the endoplasmic reticulum (ER) and a C-terminal tail in the cytosol. The authors found that two independent Drosophila mutations in the coding region of calnexin (cnx) were associated with a decrease in the abundance of rhodopsin (Rh1), the G protein-coupled receptor that activates the visual transduction pathway. The expression of other photoreceptor proteins [including Rh3, Rh4, and Rh5 opsins; chaoptin; the TRP and TRPL channels; phospholipase C-β (PLC-β); arrestins 1 and 2; and Gαq] was not affected. Although the abundance of RH1 transcripts was not affected, RH1 maturation was impaired. Cnx formed a stable complex with Rh1, and immunocytochemical analysis confirmed that, in Drosophila photoreceptors, Cnx localized to the ER. Cnx mutants also showed age-dependent retinal degeneration, which was enhanced by light and slowed by mutation of PLC-β. PLC-β, which is activated during the phototransduction cascade, stimulates the opening of TRP and TRPL, thereby eliciting the influx of calcium, which can be toxic at high concentrations. Calcium imaging revealed that the increase in intracellular calcium concentration in response to illumination was markedly greater in cnx mutant photoreceptor cells than in wild-type cells or cells with a mutation in another chaperone required for Rh1 maturation that does not have a calcium-binding domain. Thus, the authors conclude that Cnx plays a dual role in photoreceptor cells, serving not only as a Rh1 chaperone but also as a calcium buffer.
E. E. Rosenbaum, R. C. Hardie, N. J. Colley, Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and photoreceptor cell survival. Neuron 49, 229-241 (2006). [PubMed]
Citation: Calcium Turns a Blind Eye to an Unchaperoned Photoreceptor. Sci. STKE 2006, tw48 (2006).
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