INTRACELLULAR PROTEIN-TRANSPORT TO THE THYROCYTE PLASMA-MEMBRANE - POTENTIAL IMPLICATIONS FOR THYROID PHYSIOLOGY

We present a snapshot of developments in epithelial biology that may p rove helpful in understanding cellular aspects of the machinery design ed for the synthesis of thyroid hormones on the thyroglobulin precurso r. The functional unit of the thyroid gland is the follicle, delimited by a monolayer of thyrocytes. Like the cells of most simple epithelia , thyrocytes exhibit specialization of the cell surface that confronts two different extracellular environments-apical and basolateral, whic h are separated by tight junctions. Specifically, the basolateral doma in faces the interstitium/bloodstream, while the apical domain is in c ontact with the lumen that is the primary target for newly synthesized thyroglobulin secretion and also serves as a storage depot for previo usly secreted protein. Thyrocytes use their polarity in several import ant ways, such as for maintaining basolaterally located iodide uptake and T-4 deiodination, as well apically located iodide efflux and iodin ation machinery. The mechanisms by which this organization is establis hed, fall in large part under the more general cell biological problem of intracellular sorting and trafficking of different proteins en rou te to the cell surface. Nearly all exportable proteins begin their bio logical life after synthesis in an intracellular compartment known as the endoplasmic reticulum (ER), upon which different degrees of diffic ulty may be encountered during nascent polypeptide folding and initial export to the Golgi complex. In these initial stages, ER molecular ch aperones can assist in monitoring protein folding and export while the mselves remaining as resident proteins of the thyroid ER. After export from the ER, most subsequent sorting for protein delivery to apical o r basolateral surfaces of thyrocytes occurs within another specialized intracellular compartment known as the trans-Golgi network. Targeting information encoded in secretory proteins and plasma membrane protein s can be exposed or buried at different stages along the export pathwa y, which is likely to account for sorting and specific delivery of dif ferent newly-synthesized proteins. Defects in either burying or exposi ng these structural signals, and consequent abnormalities in protein t ransport, may contribute to different thyroid pathologies.