RT Journal Article
SR Electronic
T1 Constitutive Secretion of Protease Nexin-1 by Glial Cells and Its Regulation by G-Protein-Coupled Receptors
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8995
OP 9004
DO 10.1523/JNEUROSCI.2430-05.2005
VO 25
IS 39
A1 Ronald Giau
A1 Josiane Carrette
A1 Joël Bockaert
A1 Vincent Homburger
YR 2005
UL http://www.jneurosci.org/content/25/39/8995.abstract
AB 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.