Calnexin is essential for rhodopsin maturation, Ca2+ regulation, and photoreceptor cell survival

In sensory neurons, successful maturation of signaling molecules and regulation of Ca2+ are essential for cell function and survival. Here, we demonstrate a multifunctional role for calnexin as both a molecular chaperone uniquely required for rhodopsin maturation and a regulator of Ca2+ that enters...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2006-01, Vol.49 (2), p.229-241
Main Authors: Rosenbaum, Erica E, Hardie, Roger C, Colley, Nansi J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Animals, Genetically Modified
Blotting, Northern
Calcium - metabolism
Calcium Signaling - physiology
Calnexin - physiology
Cell Survival - physiology
Chromatography, Affinity
Crystal structure
Defects
Disease
DNA - biosynthesis
DNA - genetics
Drosophila
Electrophoresis, Polyacrylamide Gel
Endoplasmic reticulum
Immunohistochemistry
Insects
Light
Microscopy, Electron
Molecular Chaperones
Molecular Sequence Data
Mutation
Mutation - genetics
Mutation - physiology
Patch-Clamp Techniques
Photoreceptor Cells, Invertebrate - cytology
Photoreceptor Cells, Invertebrate - physiology
Photoreceptors
Proteins
Quality control
Retinal Degeneration - genetics
Retinal Degeneration - pathology
Rhodopsin - biosynthesis
Rhodopsin - genetics
Rhodopsin - physiology
Vertebrates
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Summary:In sensory neurons, successful maturation of signaling molecules and regulation of Ca2+ are essential for cell function and survival. Here, we demonstrate a multifunctional role for calnexin as both a molecular chaperone uniquely required for rhodopsin maturation and a regulator of Ca2+ that enters photoreceptor cells during light stimulation. Mutations in Drosophila calnexin lead to severe defects in rhodopsin (Rh1) expression, whereas other photoreceptor cell proteins are expressed normally. Mutations in calnexin also impair the ability of photoreceptor cells to control cytosolic Ca2+ levels following activation of the light-sensitive TRP channels. Finally, mutations in calnexin lead to retinal degeneration that is enhanced by light, suggesting that calnexin's function as a Ca2+ buffer is important for photoreceptor cell survival. Our results illustrate a critical role for calnexin in Rh1 maturation and Ca2+ regulation and provide genetic evidence that defects in calnexin lead to retinal degeneration.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2005.12.011