Transgene expression of prion protein induces crinophagy in intermediate pituitary cells.
The cellular form of the prion protein (PrP(C)) is a plasma membrane-anchored glycoprotein whose physiological function is poorly understood. Here we report the effect of transgene expression of Xenopus PrP(C) fused to the C-terminus of the green fluorescent protein (GFP-PrP(C)) specifically in the neuroendocrine intermediate pituitary melanotrope cells of Xenopus laevis. In the transgenic melanotrope cells, the level of the prohormone proopiomelanocortin (POMC) in the secretory pathway was reduced when the cells were (i) exposed for a relatively long time to the transgene product (by physiologically inducing transgene expression), (ii) metabolically stressed, or (iii) forced to produce unfolded POMC. Intriguingly, although the overall ultrastructure was normal, electron microscopy revealed the induction of lysosomes taking up POMC secretory granules (crinophagy) in the transgenic melanotrope cells, likely causing the reduced POMC levels. Together, our results indicate that in neuroendocrine cells transgene expression of PrP(C) affects the functioning of the secretory pathway and induces crinophagy.
van Rosmalen
Jos W G
JW
Department of Molecular Animal Physiology, Nijmegen Center for Molecular Life Sciences (NCMLS), Institute for Neuroscience, Radboud University Nijmegen, 6525 GA Nijmegen, The Netherlands.
Martens
Gerard J M
GJ
D000818:Animals; D030801:Animals, Genetically Modified; D015870:Gene Expression / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008970:Molecular Weight; D052716:Pituitary Gland, Intermediate / Q000378:metabolism / Q000648:ultrastructure*; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D011328:Prions; D029867:Xenopus Proteins; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin