A systematic evaluation of sorting motifs in the sodium–iodide symporter (NIS)

2016 ◽  
Vol 473 (7) ◽  
pp. 919-928 ◽  
Author(s):  
Elisabeth Darrouzet ◽  
Fanny Graslin ◽  
Didier Marcellin ◽  
Iulia Tcheremisinova ◽  
Charles Marchetti ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Sodium Iodide ◽  
Protein A ◽  
Systematic Evaluation ◽  
Binding Motif ◽  
Sodium Iodide Symporter ◽  
Binding Motifs ◽  
Leucine Residue

Human sodium–iodide symporter (NIS) variants were created to suppress predicted binding motifs potentially implicated in trafficking of this protein. A leucine residue in an internal PDZ-binding motif was found to be essential for expression of the symporter at the plasma membrane.

An intramolecular ionic interaction linking defective sodium/iodide symporter transport to the plasma membrane and dyshormonogenic congenital hypothyroidism

Thyroid ◽  
2021 ◽  
Author(s):  
Carlos Eduardo Bernal Barquero ◽  
Mariano Martín ◽  
Romina Celeste Geysels ◽  
Victoria Peyret ◽  
Patricia Papendieck ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Congenital Hypothyroidism ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Ionic Interaction

scholarly journals Iodide excess regulates its own efflux: a possible involvement of pendrin

2016 ◽  
Vol 310 (7) ◽  
pp. C576-C582 ◽  
Author(s):  
Jamile Calil-Silveira ◽  
Caroline Serrano-Nascimento ◽  
Peter Andreas Kopp ◽  
Maria Tereza Nunes
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Sodium Iodide ◽  
Inhibitory Effect ◽  
Membrane Insertion ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Hormone Synthesis ◽  
Rat Thyroid

Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies demonstrated that pendrin is able to mediate apical efflux of iodide in thyrocytes. Acute iodide excess transiently impairs thyroid hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect. Although the escape from this inhibitory effect is not completely understood, it has been related to the inhibition of sodium-iodide symporter-mediated iodide uptake. However, the effects of iodide excess on iodide efflux have not been characterized. Herein, we investigated the consequences of iodide excess on pendrin abundance, subcellular localization, and iodide efflux in rat thyroid PCCl3 cells. Our results indicate that iodide excess increases pendrin abundance and plasma membrane insertion after 24 h of treatment. Moreover, iodide excess increases pendrin half-life. Finally, iodide exposure also increases iodide efflux from PCCl3 cells. In conclusion, these data suggest that pendrin may have an important role in mediating iodide efflux in thyrocytes, especially under conditions of iodide excess.

Stereotyped Patterns of Somatic Hypermutation (SHM) in Subsets of Patients with Chronic Lymphocytic Leukemia (CLL): Implications for the Role of Antigen Selection in Leukemogenesis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 744-744
Author(s):  
Fiona Murray ◽  
Nikos Darzentas ◽  
Anastasia Hadzidimitriou ◽  
Gerard Tobin ◽  
Myriam Boudjogra ◽  
...  
Keyword(s):  
Somatic Hypermutation ◽  
Protein A ◽  
Specific Antigen ◽  
Lymphocytic Leukemia ◽  
Binding Motif ◽  
Staphylococcal Protein A ◽  
Binding Motifs ◽  
Mutational Status ◽  
Identity Groups

Abstract We examined SHM features in 1967 IGH rearrangements from 1939 patients with CLL. The sequences were divided into four “identity groups”; “truly unmutated” (100% identity to germline; 677 sequences), “minimally mutated” (99–99.9% identity; 133 sequences), “borderline mutated” (98–98.9% identity; 93 sequences) and “mutated” (<98% identity; 1064 sequences). At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged on analysis of subgroups of sequences. In particular, the IGHV repertoire of the four “identity groups” differed considerably, with the IGHV1-69 and IGHV1-2 genes predominating among “truly unmutated” and “minimally mutated” sequences, respectively. In contrast, other genes were mostly used in “mutated” rearrangements (eg, IGHV4-34/3-23/3-7). Of note, IGHV3-21 and IGHV3-48 had the highest proportion of “borderline mutated” rearrangements. In selected groups of sequences, a remarkable preservation of the germline configuration was observed in superantigenic binding motifs, prompting speculation that subsets of CLL cells could also receive stimulation signals by superantigenic-like interactions. In detail, the vast majority of IGHV4-34 sequences retained germline conformation at the four FR1 positions of the IGHV4-34-specific I/i binding motif. Similarly, IGHV3-21 sequences displayed remarkably few alterations of the IGHV3-specific staphylococcal protein A binding motif. Following established criteria, we identified 530/1967 sequences (27%) as belonging to 113 different subsets with stereotyped HCDR3. The distribution of sequences among subsets differed significantly according to mutational status: 43% of “truly unmutated” sequences belonged to a subset, compared to only 16% of the “mutated” group (p<0.001). Of note, among certain IGHV genes (ie, IGHV1-2/3-21/4-34/4-4), shared “stereotyped” amino acid (AA) changes (i.e. the same AA replacement at the same position) occurred across the entire IGHV sequence significantly more frequently in cases with stereotyped vs. heterogeneous HCDR3s and therefore, could be considered as “subset-biased”. Stereotyped AA changes were also observed in subsets of minimally mutated cases, indicating that even a low level of mutations may be functionally relevant. Comparison to public-database non-CLL sequences revealed that certain stereotyped AA changes were over-represented in CLL and thus could also be considered as “CLL-biased”. The very precise targeting and distinctive features of SHM in subgroups of CLL patients provide further evidence for the important role of selection by specific antigen(s) in CLL leukemogenesis.

scholarly journals Na+ coordination at the Na2 site of the Na+/I− symporter

2016 ◽  
Vol 113 (37) ◽  
pp. E5379-E5388 ◽  
Author(s):  
Giuseppe Ferrandino ◽  
Juan Pablo Nicola ◽  
Yuly E. Sánchez ◽  
Ignacia Echeverria ◽  
Yunlong Liu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Binding Sites ◽  
Sodium Iodide ◽  
The Other ◽  
Similar Function ◽  
Sodium Iodide Symporter ◽  
Whole Cells ◽  
Thyroid Hormone Biosynthesis ◽  
Hormone Biosynthesis ◽  
Medical Relevance

The sodium/iodide symporter (NIS) mediates active I− transport in the thyroid—the first step in thyroid hormone biosynthesis—with a 2 Na+: 1 I− stoichiometry. The two Na+ binding sites (Na1 and Na2) and the I− binding site interact allosterically: when Na+ binds to a Na+ site, the affinity of NIS for the other Na+ and for I− increases significantly. In all Na+-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na+ ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues—S66, D191, Q194, and Q263—are also involved in Na+ coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I−. These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance.

The PDZ protein SCRIB regulates sodium/iodide symporter (NIS) expression at the basolateral plasma membrane

2021 ◽  
Vol 35 (8) ◽  
Author(s):  
Mariano Martín ◽  
Lisa Salleron ◽  
Victoria Peyret ◽  
Romina Celeste Geysels ◽  
Elisabeth Darrouzet ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Basolateral Plasma Membrane ◽  
Pdz Protein

Identification of novel sodium iodide symporter (NIS) interactors which modulate iodide uptake

2016 ◽  
Author(s):  
Alice Fletcher ◽  
Vikki Poole ◽  
Bhavika Modasia ◽  
Waraporn Imruetaicharoenchoke ◽  
Rebecca Thompson ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake

Identification of novel sodium iodide symporter interactors which modulate iodide uptake

2017 ◽  
Author(s):  
Alice Fletcher ◽  
Vikki Poole ◽  
Bhavika Modasia ◽  
Waraporn Imruetaicharoenchoke ◽  
Rebecca Thompson ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake

An investigation into sodium-iodide symporter (NIS) dimerization and its impact on radioiodide uptake in thyroid cancer

2017 ◽  
Author(s):  
Rebecca J. Thompson ◽  
Alice Fletcher ◽  
Hannah Nieto ◽  
Mohammed Alshahrani ◽  
Katie Baker ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter

Identification of novel sodium iodide symporter (NIS) interactors which modulate radioiodine uptake

2018 ◽  
Author(s):  
Alice Fletcher ◽  
Vikki Poole ◽  
Caitlin Thornton ◽  
Kate Baker ◽  
Rebecca Thompson ◽  
...  
Keyword(s):  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Radioiodine Uptake
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