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Expression of Neuroserpin Is Linked to Neuroendocrine Cell Activation

Department of Molecular Animal Physiology, Institute for Neuroscience, Nijmegen Center for Molecular Life Sciences, Radboud University, 6525 GA Nijmegen, The Netherlands

Address all correspondence and requests for reprints to: Dr. G. J. M. Martens, Department of Molecular Animal Physiology, Institute for Neuroscience, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, Geert Grooteplein Zuid 28, 6525 GA Nijmegen, The Netherlands. E-mail: g.martens{at}ncmls.ru.nl.

Inhibitors of serine proteases (serpins) are important regulators of intracellular and extracellular proteolytic pathways, and they function by forming an irreversible complex with their substrate. Neuroserpin represents a neuroendocrine-specific serpin family member that is expressed in brain regions displaying synaptic plasticity. In this study, we explored the biosynthesis of endogenous neuroserpin in a neuroendocrine model system, namely the melanotrope cells of Xenopus intermediate pituitary. The biosynthetic activity of these cells can be physiologically manipulated (high and low production of the prohormone proopiomelanocortin in black and white animals, respectively), resulting from a synaptic plasticity in innervating hypothalamic neurons. We found that neuroserpin was also differentially expressed in the Xenopus intermediate, but not anterior, pituitary with a 3-fold higher mRNA and more than 30-fold higher protein expression in the active vs. the inactive melanotrope cells. Two newly synthesized glycosylated forms of the neuroserpin protein (47 and 50 kDa) were produced and secreted by the active cells. Intriguingly, neuroserpin was found in an approximately 130-kDa sodium dodecyl sulfate-stable complex in the active, but not in the inactive, melanotrope cells, which correlated with the high and low proopiomelanocortin expression levels, respectively. In conclusion, we report on the biosynthesis of neuroserpin in a physiological context, and we find that the induction of neuroserpin expression and the formation of the 130-kDa neuroserpin-containing complex are linked to neuroendocrine cell activation.

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