http://www.jneurosci.org/content/32/15/5186.abstract
Abstract
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.
