Glutamate controls tPA recycling by astrocytes, which in turn influences glutamatergic signals.
Tissue-type plasminogen activator (tPA) regulates physiological processes in the brain, such as learning and memory, and plays a critical role in neuronal survival and neuroinflammation in pathological conditions. Here we demonstrate, by combining mouse in vitro and in vivo data, that tPA is an important element of the cross talk between neurons and astrocytes. The data show that tPA released by neurons is constitutively endocytosed by astrocytes via the low-density lipoprotein-related protein receptor, and is then exocytosed in a regulated manner. The exocytotic recycling of tPA by astrocytes is inhibited in the presence of extracellular glutamate. Kainate receptors of astrocytes act as sensors of extracellular glutamate and, via a signaling pathway involving protein kinase C, modulate the exocytosis of tPA. Further, by thus capturing extracellular tPA, astrocytes serve to reduce NMDA-mediated responses potentiated by tPA. Overall, this work provides the first demonstration that the neuromodulator, tPA, may also be considered as a gliotransmitter.
Institut National de Santé et de Recherche Médicale, U919, Serine Proteases and Pathophysiology of Neurovascular Unit, Université de Caen, Groupement d'Internet Public Cyceron, 14073 Caen Cedex, France.
SourceThe Journal of neuroscience : the official journal of the Society for Neuroscience 32:15 2012 Apr 11 pg 5186-99
Protein Kinase C
Real-Time Polymerase Chain Reaction
Receptors, Kainic Acid
Tissue Plasminogen Activator
Tumor Suppressor Proteins
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't