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The nucleotide exchange factor activity of Grp170 may explain the non‐lethal phenotype of loss of Sil1 function in man and mouse
Author(s) -
Weitzmann Andreas,
Volkmer Jörg,
Zimmermann Richard
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.08.055
Subject(s) - endoplasmic reticulum , phenotype , mutant , guanine nucleotide exchange factor , nucleotide , mutation , gene , loss function , genetics , chaperone (clinical) , microbiology and biotechnology , chemistry , biology , medicine , signal transduction , pathology
Recent genetic work characterized homozygous mutations in the SIL1 gene as cause for the neurodegeneration that is associated with Marinesco–Sjögren syndrome in man and the woozy mouse mutant. All reported mutations were expected to result in loss of Sil1 function. Sil1 has previously been shown to act as nucleotide exchange factor for the molecular chaperone immunoglobulin heavy chain binding protein (BiP) in the lumen of the endoplasmic reticulum (ER). In the yeast ER Lhs1p was shown to be able to substitute for Sil1p and to represent an alternative nucleotide exchange activity. Therefore, by analogy the mammalian ortholog of Lhs1p, Grp170, was suggested to be able to compensate for the loss of Sil1 function in many mammalian organs. Here we characterize mammalian Grp170 as alternative nucleotide exchange factor for BiP, thus providing a likely explanation for the non‐lethal phenotype of the homozygous human and murine SIL 1 mutations.