Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-Tooth 1IA Gas3/PMP22 mutants

Alessandra Fontanini, Romina Chies, Erik L. Snapp, Moreno Ferrarini, Gian Maria Fabrizi, Claudio Brancolini

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2378-2387
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number3
DOIs
StatePublished - Jan 21 2005
Externally publishedYes

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Calnexin
Polysaccharides
Tooth
Green Fluorescent Proteins
Endoplasmic Reticulum
Hereditary Sensory and Motor Neuropathy
Photobleaching
Proteins
Peripheral Nervous System Diseases
Missense Mutation
Point Mutation
Lectins
Membrane Proteins
Cells
Mutation
Experiments

ASJC Scopus subject areas

  • Biochemistry

Cite this

Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-Tooth 1IA Gas3/PMP22 mutants. / Fontanini, Alessandra; Chies, Romina; Snapp, Erik L.; Ferrarini, Moreno; Fabrizi, Gian Maria; Brancolini, Claudio.

In: Journal of Biological Chemistry, Vol. 280, No. 3, 21.01.2005, p. 2378-2387.

Research output: Contribution to journalArticle

Fontanini, A, Chies, R, Snapp, EL, Ferrarini, M, Fabrizi, GM & Brancolini, C 2005, 'Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-Tooth 1IA Gas3/PMP22 mutants', Journal of Biological Chemistry, vol. 280, no. 3, pp. 2378-2387. https://doi.org/10.1074/jbc.M405104200
Fontanini, Alessandra ; Chies, Romina ; Snapp, Erik L. ; Ferrarini, Moreno ; Fabrizi, Gian Maria ; Brancolini, Claudio. / Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-Tooth 1IA Gas3/PMP22 mutants. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 3. pp. 2378-2387.
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