IODINATION OF MATURE CATHEPSIN-D IN THYROCYTES AS AN INDICATOR FOR ITS TRANSPORT TO THE CELL-SURFACE

Thyrocytes are known for their ability to iodinate thyroglobulin from which the thyroid hormones are generated. In the intact thyroid gland the iodination process is almost exclusively executed at the apical pl asma membrane of thyroid epithelial cells, Here, we show that freshly isolated thyrocytes iodinated polypeptides other than thyroglobulin an d that one of the major iodinated polypeptides was the mature form of the lysosomal protease cathepsin D (CD), The detection of mature CD as an iodinated polypeptide suggested that a fraction of the lysosomally maturated enzyme was delivered to the apical plasma membrane where it became available for iodination, After labeling of thyrocytes with [S -35]methionine/cysteine overnight part of the mature CD was released i nto the culture medium. This was abolished by inhibiting maturation of CD with NH4Cl, indicating that mature CD appeared in the medium after its proteolytic maturation in an acidic compartment, Besides CD other soluble lysosomal polypeptides like the beta-N-acetylhexosaminidase a nd the sphingolipid-activating protein D (Sap D) were iodinated and pa rtially secreted as mature polypeptides. In contrast, the membrane-ass ociated lysosomal ceramidase was iodinated and partially secreted as i mmature single-chain enzyme and not as fully maturated two-chain enzym e,These data indicate that a portion of mature CD and other soluble ly sosomal enzymes is delivered from lysosomes to the cell surface wherea s come membrane-associated enzymes from the terminal lysosomal compart ment are efficiently excluded from this process.