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Ljubljana, Slovenia

Rituper B.,University of Ljubljana | Davletov B.,University of Cambridge | Zorec R.,University of Ljubljana | Zorec R.,Celica Biomedical Center
Clinical Lipidology | Year: 2010

Exocytosis is a highly conserved and ubiquitous process of eukaryotic cells responsible for the release of signaling molecules into extracellular space. Exocytosis involves trafficking, docking and eventually fusion of vesicles, carrying various cargo, with the plasma membrane. Until recently, the membrane fusion was considered to be predominantly mediated by proteins such as SNAP receptors, Muncs and Rabs, where lipids only played a passive role. However, newer studies portray lipids differently. Not only do lipids have a significantly more important role in membrane merger as previously believed, they also appear to be critical for regulating the entire process of exocytosis. The purpose of this article is to highlight the importance of specific lipids and lipid-protein interactions in regulated release of neurotransmitters and hormones. © 2010 Future Medicine Ltd. Source

Gucek A.,University of Ljubljana | Vardjan N.,University of Ljubljana | Vardjan N.,Celica Biomedical Center | Zorec R.,University of Ljubljana | And 2 more authors.
Neurochemical Research | Year: 2012

Astrocytes, a type of glial cells in the brain, are eukaryotic cells, and a hallmark of these are subcellular organelles, such as secretory vesicles. In neurons vesicles play a key role in signaling. Upon a stimulus-an increase in cytosolic concentration of free Ca2+ ([Ca2+] i)-the membrane of vesicle fuses with the presynaptic plasma membrane, allowing the exit of neurotransmitters into the extracellular space and their diffusion to the postsynaptic receptors. For decades it was thought that such vesiclebased mechanisms of gliotransmitter release were not present in astrocytes. However, in the last 30 years experimental evidence showed that astrocytes are endowed with mechanisms for vesicle- and non-vesicle-βased gliotransmitter release mechanisms. The aim of this review is to focus on exocytosis, which may play a role in gliotransmission and also in other forms of cell-to-cell communication, such as the delivery of transporters, ion channels and antigen presenting molecules to the cell surface. © Springer Science+Business Media, LLC 2012. Source

Kreft M.,University of Ljubljana | Kreft M.,Celica Biomedical Center | Luksic M.,University of Ljubljana | Zorec T.M.,University of Ljubljana | And 3 more authors.
Cellular and Molecular Life Sciences | Year: 2013

Astrocytes interact with neurons and endothelial cells and may mediate exchange of metabolites between capillaries and nerve terminals. In the present study, we investigated intracellular glucose diffusion in purified astrocytes after local glucose uptake. We used a fluorescence resonance energy transfer (FRET)-based nano sensor to monitor the time dependence of the intracellular glucose concentration at specific positions within the cell. We observed a delay in onset and kinetics in regions away from the glucose uptake compared with the region where we locally super-fused astrocytes with the d-glucose-rich solution. We propose a mathematical model of glucose diffusion in astrocytes. The analysis showed that after gradual uptake of glucose, the locally increased intracellular glucose concentration is rapidly spread throughout the cytosol with an apparent diffusion coefficient (D app) of (2.38 ± 0.41) × 10-10 m2 s-1 (at 22-24 C). Considering that the diffusion coefficient of d-glucose in water is D = 6.7 × 10-10 m2 s-1 (at 24 C), D app determined in astrocytes indicates that the cytosolic tortuosity, which hinders glucose molecules, is approximately three times higher than in aqueous solution. We conclude that the value of D app for glucose measured in purified rat astrocytes is consistent with the view that cytosolic diffusion may allow glucose and glucose metabolites to traverse from the endothelial cells at the blood-brain barrier to neurons and neighboring astrocytes. © 2012 Springer Basel. Source

Prebil M.,University of Ljubljana | Jensen J.,Norwegian School of Sport Sciences | Zorec R.,University of Ljubljana | Zorec R.,Celica Biomedical Center | And 2 more authors.
Archives of Physiology and Biochemistry | Year: 2011

Astrocytes are glial cells, which play a significant role in a number of processes, including the brain energy metabolism. Their anatomical position between blood vessels and neurons make them an interface for effective glucose uptake from blood. After entering astrocytes, glucose can be involved in different metabolic pathways, e.g. in glycogen production. Glycogen in the brain is localized mainly in astrocytes and is an important energy source in hypoxic conditions and normal brain functioning. The portion of glucose metabolized into glycogen molecules in astrocytes is as high as 40%. It is thought that the release of gliotransmitters (such as glutamate, neuroactive peptides and ATP) into the extracellular space by regulated exocytosis supports a significant part of communication between astrocytes and neurons. On the other hand, neurotransmitter action on astrocytes has a significant role in brain energy metabolism. Therefore, understanding the astrocytes energy metabolism may help understanding neuron-astrocyte interactions. © 2011 Informa UK, Ltd. Source

Rituper B.,University of Ljubljana | Flasker A.,University of Ljubljana | Gucek A.,University of Ljubljana | Chowdhury H.H.,University of Ljubljana | And 4 more authors.
Cell Calcium | Year: 2012

Since the 1970s, much effort was been expended researching mechanisms of regulated exocytosis. Early work focused mainly on the role of proteins. Most notably the discovery of SNARE proteins in the 1980s and the zippering hypothesis brought us much closer to understanding the complex interactions in membrane fusion between vesicle and plasma membranes, a pivotal component of regulated exocytosis. However, most likely due to the predictions of the Singer-Nicholson fluid mosaic membrane model, the lipid components of the exocytotic machinery remained largely overlooked. Lipids were considered passive constituents of cellular membranes, not contributing much, if anything, to the process of exocytosis and membrane fusion. Since the 1990s, this so-called proteocentric view has been gradually giving way to the new perspective best described with the term proteolipidic. Many lipids were found to be of great importance in the regulation of exocytosis. Here we highlight the role of cholesterol. Furthermore, by using high-resolution cell-attached membrane capacitance measurements, we have monitored unitary exocytotic events in cholesterol-depleted membranes. We show that the frequency of these events is attenuated, providing evidence at the single vesicle level that cholesterol directly influences the merger of the vesicle and the plasma membranes. © 2012 Elsevier Ltd. Source

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