ER Reorganization is Remarkably Induced in COS-7 Cells Accumulating Transmembrane Protein Receptors Not Competent for Export from the Endoplasmic Reticulum |
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Authors: | Massimo D’Agostino Arianna Crespi Elena Polishchuk Serena Generoso Gianluca Martire Sara Francesca Colombo Stefano Bonatti |
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Affiliation: | 1. Department of Molecular medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy 2. CNR, Institute of Neuroscience and Biometra Department, University of Milan, via Vanvitelli 32, 20129, Milan, Italy 3. Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy 4. Department of Biosciences and Territory, University of Molise, Campobasso, Italy 5. Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, via S. Pansini 5, 80131, Naples, Italy
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Abstract: | The newly synthesized mutant L501fsX533 Frizzled-4 form and the alpha3beta4 nicotinic acetylcholine receptor expressed in the absence of nicotine accumulate in the endoplasmic reticulum of COS-7 cells and induce the formation of large areas of smooth and highly convoluted cisternae. This results in a generalized block of the transport to the Golgi complex of newly synthesized proteins. Intriguingly, both effects happen peculiarly in COS-7 cells; HeLa, Huh-7, and HEK293 cells expressing the two receptors at similar level than COS-7 cells show normal ER and normal transport toward the plasma membrane. These results question the conclusion that a dominant-negative mechanism would explain the dominance of the mutant L501fsX533 Fz4 allele in the transmission of a form of Familial exudative vitreoretinopathy. Moreover, they indicate that the coordination of endoplasmic reticulum homeostasis in COS-7 cells is particularly error prone. This finding suggests that COS-7 cells may be extremely useful to study the molecular mechanisms regulating endoplasmic reticulum size and architecture. |
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