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Retention of pendrin in the endoplasmic reticulum is a major mechanism for Pendred syndrome
- Source :
- Human Molecular Genetics. 11:2625-2633
- Publication Year :
- 2002
- Publisher :
- Oxford University Press (OUP), 2002.
-
Abstract
- Pendred syndrome is a major cause of congenital deafness, goiter and defective iodide organification. Mutations in the transmembrane protein, pendrin, cause diminished export of iodide from thyroid follicular cells to the colloid and are associated with the syndrome. We used green fluorescent protein (GFP) chimeras of wild-type (WT) pendrin and three common natural mutants (L236P, T416P and G384) to study their intracellular trafficking in living cells. Time-lapse imaging, dual color labeling and fluorescent recovery after photobleaching (FRAP) studies demonstrated that GFP-WT pendrin targets to the plasma membrane. In contrast, all three mutant pendrins were retained in the endoplasmic reticulum (ER) in co-localization studies with ER and Golgi markers. The ER retention of L236P appeared to be selective as this mutant did not prevent a viral membrane protein, VSVGtsO45 or wild-type pendrin from targeting the plasma membrane. These findings suggest that ER retention and defective plasma membrane targeting of pendrin mutants play a key role in the pathogenesis of Pendred syndrome.
- Subjects :
- Endoplasmic Reticulum
Follicular cell
symbols.namesake
Genes, Reporter
otorhinolaryngologic diseases
Genetics
medicine
Humans
Abnormalities, Multiple
Molecular Biology
Integral membrane protein
Genetics (clinical)
Pendred syndrome
biology
Endoplasmic reticulum
Membrane Transport Proteins
ER retention
General Medicine
Pendrin
Golgi apparatus
Viral membrane
medicine.disease
Cell biology
Protein Transport
Amino Acid Substitution
Biochemistry
Sulfate Transporters
biology.protein
symbols
Carrier Proteins
Subjects
Details
- ISSN :
- 14602083
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Human Molecular Genetics
- Accession number :
- edsair.doi.dedup.....27a747352566fea298bf46d8b06c944b