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: Alessandra Fontanini, Romina Chies, Erik L Snapp, Moreno Ferrarini, Gian Maria Fabrizi, Claudio Brancolini
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 280 Issue 3 Pg. 2378-87 (Jan 21 2005) ISSN: 0021-9258 [Print] United States
• PMID: 15537650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Myelin Proteins
• PMP22 protein, human
• Polysaccharides
• Calnexin

Topics

• Base Sequence
• Blotting, Western
• Calnexin (physiology)
• Cell Line, Tumor
• Charcot-Marie-Tooth Disease (genetics, metabolism)
• DNA Primers
• Glycosylation
• Humans
• Myelin Proteins (genetics, metabolism)
• Polysaccharides (metabolism)