Cell-type-specific and selectively induced expression of members of the p24 family of putative cargo receptors

Members of the p24 family of type I transmembrane proteins are highly abundant in transport vesicles and are thought to be involved in selective protein transport between the endoplasmic reticulum and the Golgi complex. The p24 proteins have been grouped into four subfamilies (alpha, beta, gamma, and delta) and appear to assemble into tetrameric complexes that contain only one representative from each subfamily. Here we molecularly dissected the p24 family in a single cell type, namely in the intermediate pituitary melanotrope cells of the amphibian Xenopus laevis. The biosynthetic activity of these cells for production of their major cargo protein proopiomelanocortin (POMC) can be physiologically manipulated via the process of background adaptation (similar30-fold induction, with highly active cells in black toads and virtually inactive cells in white animals). Extensive cDNA library screening revealed the identity of six p24 proteins expressed in the Xenopus melanotrope cells, namely one member of the p24alpha (alpha(3)), one of the p24beta (beta(1)), two of the p24gamma (gamma(2), gamma(3)) and two of the p24delta (delta(1), delta(2)) subfamily. Two other Xenopus p24 proteins, Xp24alpha(2) and -gamma(1), were not expressed in the melanotrope cells, pointing to cell-type specific p24 expression. Of the six melanotrope p24 proteins, the expression of four (Xp24alpha(3), -beta(1), -gamma(3) and -delta(2)) was 20- to 30-fold induced in active versus inactive melanotropes, whereas that of the other two members (Xp24gamma(2) and -delta(1)) had not or only slightly increased. The four proteins were induced only in the intermediate melanotrope cells and not in the anterior pituitary cells, and displayed similar overall tissue distributions that differed from those of Xp24gamma(1), -gamma(2) and -delta(1). Together, our results reveal that p24 expression can be cell-type specific and selectively induced, and suggest that in Xenopus melanotrope cells an alpha(3)/beta(1)/gamma(3)/delta(2) p24 complex is involved in POMC transport through the early stages of the secretory pathway.