Abstract |
nt signalling pathways regulate cell proliferation, cell fate and morphogenetic movements. Here, we demonstrate that the Frizzled (Fz) family of Wnt receptors, similarly to G-protein-coupled receptors (GPCRs), form specific homo- and hetero-oligomers. Two lines of evidence suggest that oligomerization occurs in the endoplasmic reticulum: first, a mutant allele of Fz4, encoding a truncated protein that is retained in the endoplasmic reticulum, is linked to the autosomal-dominant retinal degenerative disease, familial exudative vitreoretinopathy (FEVR). We show that this mutant form of Fz4 oligomerizes with wild-type Fz4, retains it in the endoplasmic reticulum and inhibits its signalling. Second, a derivative of Fz1 targeted to the endoplasmic reticulum traps wild-type Fz1 in the endoplasmic reticulum and blocks its signalling. These data support the hypothesis that oligomerization of mutant and wild-type Fz proteins occurs in the endoplasmic reticulum and may explain the genetic dominance of this FEVR allele.
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Authors | Ajamete Kaykas, Julia Yang-Snyder, Madeleine Héroux, Kavita V Shah, Michel Bouvier, Randall T Moon |
Journal | Nature cell biology
(Nat Cell Biol)
Vol. 6
Issue 1
Pg. 52-8
(Jan 2004)
ISSN: 1465-7392 [Print] England |
PMID | 14688793
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- FZD1 protein, human
- FZD4 protein, human
- Frizzled Receptors
- Peptide Fragments
- Proteins
- Proto-Oncogene Proteins
- Receptors, Cell Surface
- Receptors, G-Protein-Coupled
- Receptors, Neurotransmitter
- Wnt Proteins
- Zebrafish Proteins
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Topics |
- Alleles
- Animals
- COS Cells
- Endoplasmic Reticulum
(metabolism)
- Frizzled Receptors
- Genes, Dominant
(genetics)
- Humans
- Mutation
(genetics)
- Peptide Fragments
(metabolism)
- Proteins
(genetics, metabolism)
- Proto-Oncogene Proteins
(genetics, metabolism)
- Receptors, Cell Surface
- Receptors, G-Protein-Coupled
- Receptors, Neurotransmitter
(metabolism)
- Signal Transduction
(genetics)
- Vitreoretinopathy, Proliferative
(genetics)
- Wnt Proteins
- Zebrafish Proteins
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