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Role of glycosylation of ionotropic glutamate receptors in mammalian neurons
Danačíková, Šárka ; Horák, Martin (advisor) ; Kriška, Ján (referee)
Glutamate is the most abundant excitatory neurotransmitter in the mammalian central nervous system. There are two distinct types of glutamate receptors, ionotropic and metabotropic, present in the mammalian excitatory synapses. My thesis is focused on the ionotropic glutamate receptors, which play critical roles in learning and memory formation. The main subtypes of ionotropic glutamate receptors are α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. All types of the ionotropic glutamate receptors, which are assembled as tetramers, contain many glycosylation sites, which can be modified by glycans or monosaccharides. The glycans and monosaccharides attached to the ionotropic glutamate receptors have been shown to regulate key processes such as folding of the subunits, transport to the cell surface as well as their functional properties. Recent literature also suggests that many neurological and psychiatric disorders such as schizophrenia exhibit abnormal glycosylation of ionotropic glutamate receptors. Thus, understanding of the molecular mechanisms, which regulate the glycosylation of the ionotropic glutamate receptors, may be important for developing new therapies for the patients with altered functioning of the glutamatergic synapses in the...
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Role of glycosylation of ionotropic glutamate receptors in mammalian neurons
Danačíková, Šárka ; Horák, Martin (advisor) ; Kriška, Ján (referee)
Glutamate is the most abundant excitatory neurotransmitter in the mammalian central nervous system. There are two distinct types of glutamate receptors, ionotropic and metabotropic, present in the mammalian excitatory synapses. My thesis is focused on the ionotropic glutamate receptors, which play critical roles in learning and memory formation. The main subtypes of ionotropic glutamate receptors are α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate receptors. All types of the ionotropic glutamate receptors, which are assembled as tetramers, contain many glycosylation sites, which can be modified by glycans or monosaccharides. The glycans and monosaccharides attached to the ionotropic glutamate receptors have been shown to regulate key processes such as folding of the subunits, transport to the cell surface as well as their functional properties. Recent literature also suggests that many neurological and psychiatric disorders such as schizophrenia exhibit abnormal glycosylation of ionotropic glutamate receptors. Thus, understanding of the molecular mechanisms, which regulate the glycosylation of the ionotropic glutamate receptors, may be important for developing new therapies for the patients with altered functioning of the glutamatergic synapses in the...
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The influence of zinc ions on ionotropic glutamate receptors
Fraňková, Denisa ; Krůšek, Jan (advisor) ; Adámek, Pavel (referee)
Zinc is one of the most abundant divalent metal ion in the central nervous system, where it serves as regulator of many proteins (channels, receptors, pump...), product of neurosecretion or cofactor. The highest concentration of zinc in synaptic vesicles of the specific neurons, which are called zinc-containing neurons and it is subset of glutamatergic neurons. The cumulation of zinc in the synaptic neurons is arranged mostly by transporter ZnT3. A concentration of zinc in the synaptic's vesicles is about 1mmol/l and maybe higher. The zinc-containing neurons are mostly in forebrain, where create complex and neuronal network in mammalian's brain, which conect most of cerebral cortex and limbic system (Frederickson et al. 2000). Zinc is released from synapses after a stimulation (Vogt et al. 2000) and then it affects a lot of receptors, for example postsynaptic NMDA receptors (Koh & Choi 1994) and Ca2+ permeable AMPA and cainate receptors (Hong Z. Yin 1995), voltage-gated Ca2+ channels (Atar et al. 1995) and GABAA receptors (Ruiz et al. 2004). This bachelor thesis summarizes the efekt Zn2+ on the ionotropic glutamate receptors. It is mostly adressed on the NMDA receptors, which are the most affected by zinc. The first chapter is about structure of ionotropic glutamate receptors, which is followed up other...
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