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 Scopus citations


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
Issue number3
Publication statusPublished - Jan 21 2005


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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