Pendrin and anoctamin as mediators of apical iodide efflux in thyroid cells. 2015

Jamile C Silveira, and Peter A Kopp
aDivision of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA bDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

OBJECTIVE Thyroid hormones are essential for normal development, growth, and metabolism. Their synthesis occurs in thyroid follicles and requires an adequate iodide supply and a sequence of regulated biochemical steps. The uptake of iodide into thyrocytes is well characterized, but its efflux at the apical membrane is poorly understood. This review discusses potential mechanisms underlying iodide efflux with emphasis on recent developments and controversies. RESULTS The functional characterization of pendrin (PDS/SLC26A4), a multifunctional anion exchanger, suggested that it could be involved in mediating iodide efflux. This is supported by the phenotype of patients with Pendred syndrome (deafness, goiter, partial iodide organification defect), which is caused by biallelic mutations in the SLC26A4 gene, as well as functional studies. However, apical iodide efflux is also possible in the absence of pendrin, implicating the presence of at least another channel. Recently, Anoctamin 1 (TMEM16A), a calcium-activated anion channel has been identified at the apical membrane of thyrocytes and functional studies suggest that it may play a predominant role in mediating iodide efflux. CONCLUSIONS Anoctamin and pendrin are two plausible candidates as mediators of apical iodide efflux. Their relative affinity for iodide and their exact physiological role await, however, further characterization.

UI MeSH Term Description Entries
D007454 Iodides Inorganic binary compounds of iodine or the I- ion. Iodide
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D006044 Goiter, Nodular An enlarged THYROID GLAND containing multiple nodules (THYROID NODULE), usually resulting from recurrent thyroid HYPERPLASIA and involution over many years to produce the irregular enlargement. Multinodular goiters may be nontoxic or may induce THYROTOXICOSIS. Nodular Goiter,Goiters, Nodular,Nodular Goiters
D006319 Hearing Loss, Sensorineural Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM. Deafness Neurosensory,Deafness, Neurosensory,Deafness, Sensoryneural,Neurosensory Deafness,Sensorineural Hearing Loss,Sensoryneural Deafness,Cochlear Hearing Loss,Hearing Loss, Cochlear,Deafnesses, Neurosensory,Deafnesses, Sensoryneural,Neurosensory Deafnesses,Sensoryneural Deafness,Sensoryneural Deafnesses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000075369 Anoctamin-1 An anoctamin chloride channel expressed at high levels in the liver, skeletal muscle, and gastrointestinal muscles that functions in transepithelial anion transport and smooth muscle contraction. It is essential for the function of the INTERSTITIAL CELLS OF CAJAL and plays a major role in chloride conduction by airway epithelial cells and in tracheal cartilage development. TMEM16A Protein,Transmembrane Protein 16A,Anoctamin 1
D000076988 Sulfate Transporters Highly conserved families of transmembrane anion transporters that occur in both prokaryotes and eukaryotes. In humans, they are expressed by epithelial cells in a variety of tissues and participate in diverse physiologic functions such as cell motility and regulating the composition and acidity of body fluids. Some Slc13 family proteins function as sodium ion-coupled co-transporters of sulfate and other anions. Slc26 Protein,Slc26 Transporter,Sulfate Transporter,Sulphate Transporter,Slc26 Family,Slc26 Proteins,Slc26 Transporters,Solute Carrier 26 Family,Sulphate Transporters,Protein, Slc26,Transporter, Slc26,Transporter, Sulfate,Transporter, Sulphate,Transporters, Slc26,Transporters, Sulfate,Transporters, Sulphate
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013961 Thyroid Gland A highly vascularized endocrine gland consisting of two lobes joined by a thin band of tissue with one lobe on each side of the TRACHEA. It secretes THYROID HORMONES from the follicular cells and CALCITONIN from the parafollicular cells thereby regulating METABOLISM and CALCIUM level in blood, respectively. Thyroid,Gland, Thyroid,Glands, Thyroid,Thyroid Glands,Thyroids
D013963 Thyroid Hormones Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs. Thyroid Hormone,Hormone, Thyroid,Hormones, Thyroid

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