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The Journal of Neuroscience, July 15, 1998, 18(14):5333-5343
Regulated Expression of the Cell Adhesion Glycoprotein F3 in Adult Hypothalamic Magnocellular Neurons
Karin Pierre1, Geneviève Rougon2, Michèle Allard1, Renée Bonhomme1, Gianfranco Gennarini3, Dominique A. Poulain1, and Dionysia. T. Theodosis1 1 Institut National de la Santé et de la Recherche Médicale U378 Neurobiologie Morphofonctionelle, Institut François Magendie, F33077 Bordeaux Cedex, France, 2 Centre National de la Recherche Scientifique UMR 9943 Laboratoire de Génétique et Physiologie du Développement, Parc Scientifique de Luminy, F13288 Marseille Cedex 9, France, and 3 Dipartimento di Farmacologia e Fisiologia Umana, University of Bari, Bari, I 702124 Italy
F3, a glycoprotein of the immunoglobulin superfamily implicated in axonal growth, occurs in oxytocin (OT)-secreting and vasopressin (AVP)-secreting neurons of the adult hypothalamo-neurohypophysial system (HNS) whose axons undergo morphological changes in response to stimulation. Immunocytochemistry and immunoblot analysis showed that during basal conditions of HNS secretion, there are higher levels of this glycosylphosphatidyl inositol-anchored protein in the neurohypophysis, where their axons terminate, than in the hypothalamic nuclei containing their somata. Physiological stimulation (lactation, osmotic challenge) reversed this pattern and resulted in upregulation of F3 expression, paralleling that of OT and AVP under these conditions. In situ hybridization revealed that F3 expression in the hypothalamus is restricted to its magnocellular neurons and demonstrated a more than threefold increase in F3 mRNA levels in response to stimulation. Confocal and electron microscopy localized F3 in secretory granules in all neuronal compartments, a localization confirmed by detection of F3 immunoreactivity in granule-enriched fractions obtained by sucrose density gradient fractionation of rat neurohypophyses. F3 was not visible on any cell surface in the magnocellular nuclei. In contrast, in the neurohypophysis, it was present not only in secretory granules but also on the surface of axon terminals and glia and in extracellular spaces.
Taken together, our observations reveal that the cell adhesion glycoprotein F3 is colocalized with neurohypophysial peptides in secretory granules. It follows, therefore, the regulated pathway of secretion in HNS neurons to be released by exocytosis at their axon terminals in the neurohypophysis, where it may intervene in activity-dependent structural axonal plasticity.
Key words: hypothalamo-neurohypophysial system; cell adhesion molecules; plasticity; lactation; dehydration; in situ hybridization; immunocytochemistry; immunoblot analysis
Copyright © 1998 Society for Neuroscience 0270-6474/98/18145333-11$05.00/0
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