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JCI online early table of contents: July 1, 2008

KATP channel mutations

Charles A. Stanley
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Phone: (215) 590-3420; Fax: (215) 590-1605; E-mail:

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ENDOCRINOLOGY: New insight into the mechanisms underlying congential hypothyroidism

The generation of thyroid hormones, which are essential for normal development, is dependent on the proper secretion of the protein thyroglobulin. Thyroglobuin is a large protein with several distinct regions, including one known as region I-II-III and one known as the ChEL domain. Mutations in the ChEL domain have been linked to congenital hypothyroidism. However, the exact mechanisms by which these mutations alter thyroglobulin secretion are unknown. A new study by Peter Arvan and colleagues, at the University of Michigan, Ann Arbor, has revealed that ChEL seems to have two functions that enable thryroglobulin secretion it ensures region I-II-III is folded correctly and it escorts the correctly folded protein out of the cell. The authors hope that these insights into the functions of the ChEL domain of thyroglobulin might help uncover new potential therapeutic targets for the treatment of congenital hypothyroidism.

TITLE: The cholinesterase-like domain of thyroglobulin functions as an intramolecular chaperone

Peter Arvan
University of Michigan, Ann Arbor, Michigan, USA.
Phone: (734) 936-5006; Fax: (734) 936-6684; Email:

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Contact: Karen Honey
Journal of Clinical Investigation

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