title: Analysis of cellular localization and function of carboxy-terminal mutants of pendrin.
abstract: BACKGROUND
  Iodide uptake at the basolateral membrane and iodide efflux at the apical membrane of thyrocytes, essential steps in the biosynthesis of thyroid hormone, are stimulated by thyroid stimulating hormone (TSH). Pendrin (SLC26A4) is inserted into the apical membrane of thyrocytes and thought to be involved in mediating iodide efflux.
  
  
  METHODS
  We determined the effects of carboxy-terminal mutations of pendrin on the cellular localization and the ability to transport iodide.
  
  
  RESULTS
  After exposure to forskolin, the membrane abundance of wild type pendrin and iodide efflux increase. Truncation mutants lead to complete intracellular retention. Elimination of the distal part of the sulfate transporter and antisigma factor antagonist (STAS) domain with retention of the putative protein kinase A (PKA) phosphorylation site (RKDT 714-717) results in residual membrane insertion and a partial loss of function. Deletion of the PKA site results in decreased basal function and membrane insertion and abolishes the response to forskolin.
  
  
  CONCLUSIONS
  Pendrin membrane abundance and its ability to mediate iodide efflux increase after activation of the PKA pathway. Elimination of the PKA site abolishes the response to forskolin but partial basal function and membrane insertion are maintained.
authors: Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 606011, USA.
authors: Aigerim
authors: A
authors: Bizhanova
authors: Teng-Leong
authors: TL
authors: Chew
authors: Satya
authors: S
authors: Khuon
authors: Peter
authors: P
authors: Kopp
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D006801:Humans; D007454:Iodides / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D000076988:Sulfate Transporters
chemical_list: D007454:Iodides; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D017868:Cyclic AMP-Dependent Protein Kinases