title: Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-tooth 1A Gas3/PMP22 mutants.
abstract: Missense point mutations in Gas3/PMP22 are responsible for the peripheral neuropathies Charcot-Marie-Tooth 1A and Dejerine Sottas syndrome. These mutations induce protein misfolding with the consequent accumulation of the proteins in the endoplasmic reticulum and the formation of aggresomes. During folding, Gas3/PMP22 associates with the lectin chaperone calnexin. Here, we show that calnexin interacts with the misfolded transmembrane domains of Gas3/PMP22, fused to green fluorescent protein, in a glycan-independent manner. In addition, photobleaching experiments in living cells revealed that Gas3/PMP22-green fluorescent protein mutants are mobile but diffuse at almost half the diffusion coefficient of wild type protein. Our results support emerging models for a glycan-independent chaperone role for calnexin and for the mechanism of retention of misfolded membrane proteins in the endoplasmic reticulum.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biomediche, Sezione di Biologia and MATI Center of Excellence, Universitá di Udine, Piazza le Kolbe 4, 33100 Udine, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fontanini
authors.forename: Romina
authors.initials: R
authors.lastname: Chies
authors.forename: Erik L
authors.initials: EL
authors.lastname: Snapp
authors.forename: Moreno
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fabrizi
authors.forename: Claudio
authors.initials: C
authors.lastname: Brancolini
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D037281:Calnexin / Q000502:physiology*; D045744:Cell Line, Tumor; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D006031:Glycosylation; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D009185:Myelin Proteins; C073687:PMP22 protein, human; D011134:Polysaccharides; D037281:Calnexin