Retention of pendrin in the endoplasmic reticulum is a major mechanism for Pendred syndrome

Pnina Rotman-Pikielny, Koret Hirschberg, Padma Maruvada, Koichi Suzuki, Ines E. Royaux, Eric D. Green, Leonard D. Kohn, Jennifer Lippincott-Schwartz, Paul M. Yen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)2625-2633
Number of pages9
JournalHuman Molecular Genetics
Issue number21
StatePublished - 1 Oct 2002


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