Functional diversity among p24 subfamily members

Background information. The p24 protein family plays an important but unclear role at the ER (endoplasmic reticulum)-Golgi interface. A p24 member from each subfamily (p24 alpha(3), beta(1), gamma(3) and delta(2)) is upregulated with the prohormone POMC (pro-opiomelanocortin) when Xenopus laevis intermediate pituitary melanotrope cells are physiologically activated. Here we explored the role of p24 by generating and analysing Xenopus with melanotrope cell-specific transgene expression of p24 beta(1) or p24 gamma(3), two of the p24 proteins coexpressed with POMC, and compared the results with those previously reported for the two other coexpressed p24s (p24 alpha(3) and p24 delta(2)). Results. The transgene expression of p24 beta(1) or p24 gamma(3) did not affect the endogenous p24 proteins or affected only endogenous p24 gamma(3) respectively, whereas in transgenics expressing p24 alpha(3) and p24 delta(2), the levels of all endogenous p24 proteins were strongly decreased. Nevertheless, as for p24 alpha(3) but albeit to a lesser extent, in the p24 beta(1)-transgenic melanotrope cells the rate of cargo cleavage was reduced, probably reflecting reduced cargo transport from the ER, and POMC glycosylation and sulfation in the Golgi were not affected. The p24 gamma(3)-transgenic cells displayed features of both the p24 alpha(3)-transgenics (reduced cargo cleavage, normal POMC sulfation) and the p24 delta(2)-transgenics (affected POMC glycosylation). Conclusions. Our results show that the four upregulated proteins p24 alpha(3), beta(1), gamma(3) and delta(2) have non-redundant roles in the early secretory pathway, and suggest that each p24 subfamily member provides a proper ER/Golgi subcompartmental microenvironment, together allowing correct secretory protein transport and processing.