Disparate effects of p24alpha and p24delta on secretory protein transport and processing.
BACKGROUND
The p24 family is thought to be somehow involved in endoplasmic reticulum (ER)-to-Golgi protein transport. A subset of the p24 proteins (p24alpha(3), -beta(1), -gamma(3) and -delta(2)) is upregulated when Xenopus laevis intermediate pituitary melanotrope cells are physiologically activated to produce vast amounts of their major secretory cargo, the prohormone proopiomelanocortin (POMC).


RESULTS
Here we find that transgene expression of p24alpha(3 )or p24delta(2) specifically in the Xenopus melanotrope cells in both cases causes an effective displacement of the endogenous p24 proteins, resulting in severely distorted p24 systems and disparate melanotrope cell phenotypes. Transgene expression of p24alpha(3) greatly reduces POMC transport and leads to accumulation of the prohormone in large, ER-localized electron-dense structures, whereas p24delta(2)-transgenesis does not influence the overall ultrastructure of the cells nor POMC transport and cleavage, but affects the Golgi-based processes of POMC glycomaturation and sulfation.


CONCLUSIONS
Transgenic expression of two distinct p24 family members has disparate effects on secretory pathway functioning, illustrating the specificity and non-redundancy of our transgenic approach. We conclude that members of the p24 family furnish subcompartments of the secretory pathway with specific sets of machinery cargo to provide the proper microenvironments for efficient and correct secretory protein transport and processing.
Strating
Jeroen R P M
JR
Department of Molecular Animal Physiology, Nijmegen Centre for Molecular Life Sciences, Institute for Neuroscience, Faculty of Science, Radboud University, Nijmegen, The Netherlands.
Bouw
Gerrit
G
Hafmans
Theo G M
TG
Martens
Gerard J M
GJ
D000818:Animals; D030801:Animals, Genetically Modified; D005260:Female; D006801:Humans; D008297:Male; D052717:Melanotrophs / Q000378:metabolism / Q000648:ultrastructure; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000378:metabolism
D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D029867:Xenopus Proteins; D011333:Pro-Opiomelanocortin