Exocytosis and gliocrine astroglia

Published on September 28, 2023   51 min

A selection of talks on Physiology & Anatomy

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My name is Robert Zorec. I'm from Ljubljana. Today I will talk about exocytosis in astrocytes.
I would like to highlight that this is a follow up of a previous lecture on the properties of exocytosis in astrocytes that was recorded in 2014. Let me tell you that our lab is studying pathophysiology at the subcellular level, including vesicles. That actually brings us to the topic that, in fact, our aim is to translate. So, we want to gain knowledge of studying membrane fusion and vesicle dynamics, and then the gain results we hope to be employed in translating this to medicines. In the field of cancer, we have already developed a lysosomal heterologous fusion cell-based immunotherapy to treat cancer. This therapy is already available and it is approved in Slovenia, and this was done after following a clinical trial. In the domain of neurological indications, we would like to understand vesicle-based signaling and metabolism in astrocytes, which is then a platform from which we'd like to develop small molecules that target neuroglial aerobic glycolosis to be used in treating various disorders, including neurodegeneration and neurodevelopment. This is the foreground for the lecture today.
The first message is that like in neurons, calcium-dependent exocytosis exists in astrocytes, it is controlled by SNARE proteins and cholesterol, but is very very slow. Astrocytes act as signal integrators and adaptation to regulate homeostatic processes in a slow time domain, as is the case in the endocrine system, brings us to the term: the gliocrine system. So, astrocytes are part of this very slow regulating system, hence called the gliocrine system. Astrocytes secrete neurotransmitters and a wide array of neuromodulators, hormones, metabolic, trophic, and plastic factors. The release of these gliosignals from astrocytes occurs through distinct pathways that include diffusion, plasmalemmal channels, translocation by multiple transporters and vesicle-based regulated exocytosis. That is the topic of our lecture today. These vesicles in astrocytes are of different sizes. At the end, I'd like to highlight that lysosomal vesicle traffic is altered in reactive astrocytes.