title: Functional diversity among p24 subfamily members.
abstract: BACKGROUND
  The p24 protein family plays an important but unclear role at the ER (endoplasmic reticulum)-Golgi interface. A p24 member from each subfamily (p24alpha(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 p24beta(1) or p24gamma(3), two of the p24 proteins coexpressed with POMC, and compared the results with those previously reported for the two other coexpressed p24s (p24alpha(3) and p24delta(2)).
  
  
  RESULTS
  The transgene expression of p24beta(1) or p24gamma(3) did not affect the endogenous p24 proteins or affected only endogenous p24gamma(3) respectively, whereas in transgenics expressing p24alpha(3) and p24delta(2), the levels of all endogenous p24 proteins were strongly decreased. Nevertheless, as for p24alpha(3) but albeit to a lesser extent, in the p24beta(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 p24gamma(3)-transgenic cells displayed features of both the p24alpha(3)-transgenics (reduced cargo cleavage, normal POMC sulfation) and the p24delta(2)-transgenics (affected POMC glycosylation).
  
  
  CONCLUSIONS
  Our results show that the four upregulated proteins p24alpha(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.
authors.affiliation: Department of Molecular Animal Physiology, Donders Centre for Neuroscience and Nijmegen Centre for Molecular Life Sciences (NCMLS), Faculty of Science, Radboud University, 6525 GA Nijmegen, The Netherlands.
authors.forename: Jeroen R P M
authors.initials: JR
authors.lastname: Strating
authors.forename: Theo G M
authors.initials: TG
authors.lastname: Hafmans
authors.forename: Gerard J M
authors.initials: GJ
authors.lastname: Martens
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D052717:Melanotrophs / Q000378:metabolism / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D010455:Peptides; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D011333:Pro-Opiomelanocortin