PT  - JOURNAL ARTICLE
AU  - Frédéric Cassé
AU  - Isabelle Bardou
AU  - Lydia Danglot
AU  - Aurélien Briens
AU  - Axel Montagne
AU  - Jérôme Parcq
AU  - Anuradha Alahari
AU  - Thierry Galli
AU  - Denis Vivien
AU  - Fabian Docagne
TI  - Glutamate Controls tPA Recycling by Astrocytes, Which in Turn Influences Glutamatergic Signals
AID  - 10.1523/JNEUROSCI.5296-11.2012
DP  - 2012 Apr 11
TA  - The Journal of Neuroscience
PG  - 5186--5199
VI  - 32
IP  - 15
4099  - http://www.jneurosci.org/content/32/15/5186.short
4100  - http://www.jneurosci.org/content/32/15/5186.full
SO  - J. Neurosci.2012 Apr 11; 32
AB  - 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.