Regulation of the cellular transport and compactation of thyroglobulin

The cellular transport ot thyroglobulin in thyrocytes is a TSH-regulated process and characterized by a bidirectional export-, storage- and recapture pathway. The regulation of single steps in this pathway is unclear, but a possible basis for this transport appeared to be the presence of the lysosomal targetting, signal mannose-6-phosphate (M6P), on porcine thyroglobulin and the detection of the cation-dependent M6P-receptor on the apical cell surface and the Golgi-complex in thyrocytes. The question arose, why thyroglobulin is not directed on an intracellular pathway to lysosomes thereby following the route characteristic of lysosomal enzymes. Recent observations have shown that the affinity of thyroglobulin to the M6P-receptor is very low and the receptor is presumably not effective in thyrocytes to direct thyroglobulin to lysosomes. Instead, a low affinity binding site for thyroglobulin has been found to operate on the surface of thyrocytes. This receptor is specific for thyroglobulin and is saturable at 8-13 mg thyroglobulin per ml (5-9 microM). The highest affinity of thyroglobulin was that to itself which is the basis for the positive cooperation observed during binding of thyroglobulin to thyrocyte membranes. The receptor has a relative molecular mass of 46 kDa but is not identical with the cation-dependent M6P-receptor. Because of the high-thyroglobulin-concentration in the follicle lumen (100-400 mg/ml) it has always been argued that there is no need for the presence of a thyroglobulin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)