title: ER reorganization is remarkably induced in COS-7 cells accumulating transmembrane protein receptors not competent for export from the endoplasmic reticulum.
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.
authors.affiliation: Department of Molecular medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Agostino
authors.forename: Arianna
authors.initials: A
authors.lastname: Crespi
authors.forename: Elena
authors.initials: E
authors.lastname: Polishchuk
authors.forename: Serena
authors.initials: S
authors.lastname: Generoso
authors.forename: Gianluca
authors.initials: G
authors.lastname: Martire
authors.forename: Sara Francesca
authors.initials: SF
authors.lastname: Colombo
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonatti
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure*; D051157:Frizzled Receptors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D009154:Mutation / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; C498581:Fzd4 protein, mouse; D011978:Receptors, Nicotinic; C403530:nicotinic receptor alpha3beta4
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