Incomplete posttranslational prohormone modifications in hyperactive neuroendocrine cells
1 Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, and Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen, RT 282, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands
2 Current address: Heidelberg University Biochemistry Center (BZH), Im Neuenheimer Feld 328 - #224, D-69120 Heidelberg, Germany
BMC Cell Biology 2009, 10:35 doi:10.1186/1471-2121-10-35Published: 7 May 2009
In black-background-adapted Xenopus laevis, the intermediate pituitary melanotrope cells are hyperactive, producing large amounts of their major secretory cargo proopiomelanocortin (POMC, representing ~80% of all newly synthesised proteins), whereas in white-adapted frogs these cells are only basally active. Here we explored in the hyperactive and basally active melanotrope cells the capacity for posttranslational POMC processing events in the secretory pathway.
We found that the hyperactive cells produced mainly non-complex N-glycosylated POMC, whereas in the basally active cells POMC was mostly complex N-glycosylated. Furthermore, the relative level of POMC sulphation was ~5.5-fold lower in the hyperactive than in the basally active cells. When the cargo load in the secretory pathway of the hyperactive cells was pharmacologically reduced, the relative amount of complex glycosylated POMC markedly increased.
Collectively, our data show that the secretory pathway in hyperactive neuroendocrine secretory cells lacks the capacity to fully comply with the high demands for complex glycosylation and sulphation of the overload of secretory cargo. Thus, a hyperactive secretory cell may run short in providing an output of correctly modified biological signals.