Title of my talk: Mechanisms of regulating astrocytic glutamate transporter GLT-1 trafficking.
Abstract: Astrocytes together with oligodendrocytes and microglia form three main categories of glial cells in the central nervous system (CNS). They are found throughout the brain and occupy around a half of the brain volume. Astrocytes play many roles in the brain and are critical for its proper function but they have also been implicated in majority of CNS disorders. Arguably, one of the most important functions of astrocytes in the brain is glutamate uptake from the synaptic cleft, which is ensured by glutamate transporters – mainly GLT-1. GLT-1 is highly expressed in astrocytes which compensate for its slow transport rate. It has been found that GLT-1 are highly mobile on the surface of astrocytes however mechanisms regulating this trafficking are not well understood. We have used live-cell imaging of astrocytes in mixed culture as well as in organotypic slices to study the mechanisms regulating GLT-1 surface diffusion. We constructed GLT1-pHluorin probe to study surface fraction of GLT-1 and using fluorescence recovery after fotobleaching (FRAP) we confirmed neuronal-activity-dependence in GLT-1 diffusion. We have shown that the increase in surface trafficking depends on Ca2+ signalling and is regulated by dephosphorylation of proteins and C-terminus interactions of GLT-1. Altogether these data show how Ca2+ signalling in astrocytes can participate in shaping of glutamatergic synaptic transmission.
|21/09/2010||PhD degree at Utrecht University, Netherlands, supervised by Prof. Leszek Kaczmarek (The Nencki Institute, Poland) and Prof. Johannes L. Bos (Utrecht University; Netherlands).
|3/2017 – present||Research Associate; The Nencki Institute, Warsaw, Poland; group of Prof. Leszek Kaczmarek; project: “Localization of Ca2+ signals involved in gliotransmitter release”|
|4/2011 – 3/2017||Postdoc; University College London; group of Prof. Dmitri Rusakov; projects: “Glial Glutamate Transporters Trafficking in Hippocampus”; “Spike-Driven Glutamate Electrodiffusion”; “Glutamate signalling in human neutrophils”|
|10/2010 – 3/2011||Research assistant; The Nencki Institute, Warsaw, Poland; group of Prof. Leszek Kaczmarek; project: „Influence of MMP-9 on Dendritic Spines”|
|10/2003 – 9/2010||PhD student; The Nencki Institute, Warsaw, Poland; group of Prof. Leszek Kaczmarek; project: „Matrix Metalloproteinase-9 (MMP-9) at the Synapse: Functions and Targets”|
|2007 – 2008
(total – five months)
|Visiting researcher; University Bordeaux-2, France, Department “Physiologie cellulaire de la synapse”, in group of Prof. Daniel Choquet; project: „MMP-9 Influence on NMDA Receptors’ Lateral Diffusion”|