Constitutive secretion of protease nexin-1 by glial cells and its regulation by G-protein-coupled receptors.
Extracellular serine proteases and their inhibitors (serpins) play a key role for synaptic plasticity in the developing and adult CNS. Serpins also counteract the extravasated proteases during brain injury. We studied the mechanisms by which one of the most important serpins, serpinE2 or protease nexin-1 (PN-1), is secreted by glial cells and how its secretion is regulated by extracellular signals. Using time-lapse videomicroscopy and biochemical methods, we demonstrate that PN-1 is constitutively secreted through small vesicles animated by a discontinuous movement using microtubules as tracks. The F-actin network underneath the plasma membrane acting as a barrier hindered PN-1 vesicle exocytosis. Vasointestinal/pituitary adenylate cyclase peptides and the G-protein activator mastoparan increased PN-1 secretion by disrupting the F-actin barrier. The receptor-mediated regulation of PN-1 constitutive secretion may be an important mechanism adapting extracellular proteolytic activity to synaptic activity.
Giau
Ronald
R
Unité Mixte de Recherche, Centre National de la Recherche Scientifique 5203, U 661 Institut National de la Santé et de la Recherche Médicale, Université Montpellier I, F-34094 Montpellier Cedex 5, France.
Carrette
Josiane
J
Bockaert
Joël
J
Homburger
Vincent
V
D000199:Actins / Q000187:drug effects / Q000502:physiology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D005089:Exocytosis; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D058255:Protease Nexins; D021381:Protein Transport; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism; D014018:Tissue Distribution; D014862:Wasp Venoms / Q000494:pharmacology; D021601:trans-Golgi Network / Q000378:metabolism
D000199:Actins; D016564:Amyloid beta-Protein Precursor; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D010455:Peptides; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018005:Receptors, Vasoactive Intestinal Peptide; D011993:Recombinant Fusion Proteins; C513045:Tgoln2 protein, rat; D014862:Wasp Venoms; D049452:Green Fluorescent Proteins; C037500:mastoparan