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

@article{Martn2021ThePP,
  title={The PDZ protein SCRIB regulates sodium/iodide symporter (NIS) expression at the basolateral plasma membrane},
  author={Mariano Mart{\'i}n and Lisa Salleron and Victoria Peyret and Romina Celeste Geysels and Elisabeth Darrouzet and Sabine Lindenthal and Carlos Eduardo Bernal Barquero and Ana Mar{\'i}a Masini-Repiso and Thierry Pourcher and Juan Pablo Nicola},
  journal={The FASEB Journal},
  year={2021},
  volume={35},
  url={https://api.semanticscholar.org/CorpusID:235698589}
}
Novel findings derived from the thorough characterization of the nonsense NIS mutant p.R636* NIS are reported, which provide insights into the molecular mechanisms that regulate NIS expression at the plasma membrane, a topic of great interest in the thyroid cancer field considering the relevance of NIS‐mediated radioactive iodide therapy for differentiated thyroid carcinoma.
View on Wiley
ncbi.nlm.nih.gov
10 Citations
Background Citations
5

10 Citations

The master role of polarized NIS expression in regulating iodine metabolism in the human body

Understanding the regulation and manipulating gastrointestinal iodide recirculation could increase radioiodine availability during theranostic NIS applications and lead to more efficient iodide trapping by the thyroid gland.

Silent but Not Harmless: A Synonymous SLC5A5 Gene Variant Leading to Dyshormonogenic Congenital Hypothyroidism

This work has identified the first exonic synonymous SLC5A5 gene variant causing aberrant NIS pre-mRNA splicing, thus expanding the mutational landscape of the S LC5A 5 gene leading to dyshormonogenic congenital hypothyroidism.

Targeted Next-Generation Sequencing of Congenital Hypothyroidism-Causative Genes Reveals Unexpected Thyroglobulin Gene Variants in Patients with Iodide Transport Defect

A targeted next-generation sequencing assessment of congenital hypothyroidism-causative genes in a cohort of nine unrelated pediatric patients revealed unexpected findings regarding the genetics of congenitals iodide transport defects, supporting the existence of yet to be discovered mechanisms involved in thyroid hormonogenesis.

Targeting GLI1 Transcription Factor for Restoring Iodine Avidity with Redifferentiation in Radioactive-Iodine Refractory Thyroid Cancers

It is found that GLI1 knockdown can revert iodine non-avid thyroid cancers to iodine avid cancers by increasing expression of thyroid-specific proteins, and targeting GLI 1 can be a potential therapeutic target of radioactive-iodine resistant thyroid cancers.

HIF‐1α regulates the cell viability in radioiodine‐resistant papillary thyroid carcinoma cells induced by hypoxia through PKM2/NF‐κB signaling pathway

It is demonstrated that siHIF‐1α reduces cell viability in PTC cells and rat models, while also mediating the nuclear factor‐κB (NF‐κB)/PKM2 signaling pathway.

Targeted Next-Generation Sequencing of Congenital Targeted Next-Generation Sequencing of Congenital Hypothyroidism-causative Genes Reveals Unexpected Hypothyroidism-causative Genes Reveals Unexpected Thyroglobulin Gene Variants in Patients with Iodide Transport Thyroglobulin Gene Variants in Patient

A targeted next-generation sequencing assessment of congenital hypothyroidism-causative genes in a cohort of nine unrelated pediatric patients revealed unexpected findings regarding the genetics of congenitals iodide transport defects, supporting the existence of yet to be discovered mechanisms involved in thyroid hormonogenesis.

MotSASi: Functional Short Linear Motifs (SLiMs) prediction based on genomic single nucleotide variants and structural data

The results show that inclusion of variant and sequence information significantly improves both prediction of true SLi Ms and rejection of false positives, while also allowing better classification of variants inside SLiMs, a results with a direct impact in clinical genomics.

MotSASi: Functional short linear motifs (SLiMs) prediction based on genomic single nucleotide variants and structural data.

Advances in the molecular mechanism and targeted therapy of radioactive-iodine refractory differentiated thyroid cancer

This article mainly focuses on sodium iodide symporter changes leading to the main molecular mechanisms in radioactive-iodine refractory differentiated thyroid cancer, some targeted drug resistance mechanisms and promising new treatments.

MOLECULAR MECHANISMS UNDERLYING SODIUM IODIDE SYMPORTER EXPRESSION AT THE PLASMA MEMBRANE IN THE THYROID FOLLICULAR CELL

59 References

The iodide transport defect-causing Y348D mutation in the Na+/I- symporter (NIS) renders the protein intrinsically inactive and impairs its targeting to the plasma membrane.

Y348D NIS is only partially glycosylated, is retained intracellularly, and is intrinsically inactive, consistent with the homology model's prediction that Y348 should face the side opposite the TMS9 residues that coordinate Na+ and participate in Na+ transport, and with the notion that Y 348 interacts only with hydrophobic residues.

A Carboxy-Terminal Monoleucine-Based Motif Participates in the Basolateral Targeting of the Na+/I- Symporter.

It is shown that the intracellularly facing carboxy-terminus of NIS is required for the transport of the protein to the plasma membrane, and a highly conserved monoleucine-based sorting motif that determines NIS basolateral expression is identified.

Asn441 plays a key role in folding and function of the Na+/I– symporter (NIS)

A thorough characterization of the ITD‐causing NIS mutation in which the sixth intracellular loop residues 439‐443 are missing is reported, and it is proposed that the side chain of N441, a residue conserved throughout most of the SLC5 family, interacts with the main chain amino group of G444, capping the α‐helix of transmembrane segment XII and thus stabilizing the structure of the molecule.

The iodide-transport-defect-causing mutation R124H: a &dgr;-amino group at position 124 is critical for maturation and trafficking of the Na+/I− symporter

It is concluded that the interaction between IL-2 and IL-6 is critical for the local folding required for NIS maturation and plasma membrane trafficking.

Targeting novel sodium iodide symporter interactors ADP-ribosylation factor 4 (ARF4) and valosin-containing protein (VCP) enhances radioiodine uptake: Targeting NIS interactors to enhance radioiodine uptake

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

It is found that several sites on human NIS play a role in protein stability and/or targeting to the membrane, and the most drastic effect is associated with the mutation of an internal PDZ-binding motif at position 121 that completely abolishes NIS expression at the plasma membrane.

A novel mechanism of sodium iodide symporter repression in differentiated thyroid cancer

An entirely novel mechanism by which the proto-oncogene PBF binds NIS and alters its subcellular localisation, thereby regulating its ability to uptake iodide is presented.

Implications of Na+/I- Symporter Transport to the Plasma Membrane for Thyroid Hormonogenesis and Radioiodide Therapy

Current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell is discussed, a topic of great interest in the thyroid cancer field.

The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance.

The discovery of endogenous NIS expression in more than 80% of human breast cancer samples has raised the possibility that radioiodide may be a valuable novel tool in breast cancer diagnosis and treatment.

Characterisation of the purified human sodium/iodide symporter reveals that the protein is mainly present in a dimeric form and permits the detailed study of a native C-terminal fragment.

...