In astrocytes, as in other eukaryotic cells, vesicles have key cellular functions including constitutive housekeeping of the plasma membrane structure and cell-to-cell communication. On the one hand, vesicle traffic is associated with cell surface morphology exhibiting distinct glial microdomains. These determine the signaling potential and metabolic support for neighboring cells. On the other hand, vesicles are used in astrocytes for the release of vesicle-laden chemical messengers. This lecture will address the properties of membranebound vesicles that store gliotransmitters (glutamate, adenosine 5′-triphosphate (ATP), peptides), other recycling vesicles, and endocytotic vesicles that are involved in the traffic of plasma membrane receptors such as the class II major histocompatibility molecules (MHC-II) and membrane transporters (aquaporin 4 (AQP4) and excitatory amino acid transporter 2 (EAAT2)). Vesicle dynamics greatly depends on intermediate filaments therefore one has to consider that altered vesicle dynamics may be associated with the diseases such as amyotrophic lateral sclerosis, multiple sclerosis, autistic disorders, Alzheimer’s disease, trauma, edema, and states in which astrocytes contribute to neuroinflammation. In multiple sclerosis, for example, fingolimod, a recently introduced drug, apparently also affects vesicle traffic and gliotransmitter release from astrocytes, indicating that this process may well be used as a new physiologic target for the development of new therapies.
B.04 Guest lecture
COBISS.SI-ID: 30886617In immune-mediated diseases of the central nervous system (CNS), astrocytes exposed to interferon-γ (IFN-γ) express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs. The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-γ activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor546-dextran labeling of late endosomes/lysosomes in IFN-γ treated cells was used to characterize the motion of MHC class II vesicles. Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-γ induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor546-conjugated dextran. Live imaging revealed faster mobility of dextranpositive vesicles in IFN-γ-treated versus the untreated astrocytes. Vesicle mobility was reduced in IFN-γ-treated IF-deficient astrocytes in comparison with WT astrocytes. Thus, the IFN-γ-induced increase in the mobility of MHC class II compartments is IF-dependent. Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the upregulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface.
B.06 Other
COBISS.SI-ID: 30887129