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The influence of heterodimezation of splicing variants of metobotropic glutamate receptor 1a and 1b on the intracellular distribution of receptor complexes
Dvořáková, Michaela ; Konvalinka, Jan (advisor) ; Vaněk, Ondřej (referee)
L-glutamate is a major excitatory neurotransmitter in vertebrate central nervous system. L-glutamate enables synaptic transmission through ionotropic and metabotropic glutamate receptors. These receptors are indispensable in the brain. The main role of metabotropic glutamate receptors is to mediate slow excitatory and inhibitory responses by activation of intracellular messengers and to regulate cationic channels. Metabotropic glutamate receptors are involved in synaptic plasticity, different types of memory, learning, motoric coordination and neural development. On the other hand excitotoxicity of glutamate is often associated with neurodegenerative processes such as Alzheimer, Huntington and Parkinson disease. Metabotropic glutamate receptors are promising therapeutic targets for a treatment of psychiatric and neurological diseases. Targeted trafficking of metabotropic glutamate receptors to distinct parts of neurons is influenced by neuronal polarity and thus regulates sensing and transmission of extracellular signals. Newly detected heterodimeric receptors might be trafficked in a different way than homodimers and therefore our knowledge of molecular pathways of these complexes could help us with subsequent drug targeting. This work confirms heterodimerization of metabotropic glutamate receptor 1 into...
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Role of proteins associated with the Cannabinoid receptor 1 in endocannabinoid signaling
Vozárová, Denisa ; Blahoš, Jaroslav (advisor) ; Novotný, Jiří (referee)
To preserve homeostasis and proper function in every living organism, it is important for cells to communicate with each other and their environment. Cells are constantly processing a huge amount of extracellular stimuli through proteins called receptors. Receptors can transduce the signal from extracellular to intracellular compartments. G- protein coupled receptors are the biggest group, in which also belongs Cannabinoid receptor type 1 (CB1R). Endocannabinoid system regulates many biological processes such as learning, food intake, and movement. Obesity is a serious issue nowadays and in cases of claryfing its molecular-genetic basis, there was found Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 has a role in the regulation of energetic balance and its overexpression is leading to a development of obesity. SGIP1 was detected as an interaction partner of CB1R and it had been found that it is involved in internalization via clathrin-mediated endocytosis (CME). Key proteins for initiation and early phase of CME are FCHO1/2, with which SGIP1 shares high sequential homology. However, effect of SGIP1 on internalization of activated CB1R is inhibitory unlike FCHO1/2,wheras detailed mechanism of its function remains unclear. The aim of this...
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Role of proteins associated with the cannabinoid receptor 1 in endocannabinoid signaling
Vozárová, Denisa ; Blahoš, Jaroslav (advisor) ; Novotný, Jiří (referee)
To preserve homeostasis and proper function in every living organism, it is important for cells to communicate with each other and their environment. Cells are constantly processing a huge amount of extracellular stimuli through proteins called receptors. Receptors can transduce the signal from extracellular to intracellular compartments. G-protein coupled receptors are the biggest group, in which also belongs Cannabinoid receptor type 1 (CB1R). Endocannabinoid system regulates many biological processes such as learning, food intake, and movement. Obesity is a serious issue nowadays and in cases of searching for candidate molecules, there was found Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 (SGIP1). SGIP1 has a role in the regulation of energetic balance and its overexpression is leading to a development of obesity. SGIP1 was detected as an interaction partner of CB1R and it had been found that it is involved in internalization via clathrin-mediated endocytosis. SGIP1 is very homological with FCHO1/2 - important proteins which participate on early stages of endocytosis. Mechanism of inhibitory effect of SGIP1 on internalization remains unclear. The aim of this study is to clarify the role of distinct domains of SGIP1 in context of endocytosis. Key...
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The influence of heterodimezation of splicing variants of metobotropic glutamate receptor 1a and 1b on the intracellular distribution of receptor complexes
Dvořáková, Michaela ; Konvalinka, Jan (advisor) ; Vaněk, Ondřej (referee)
L-glutamate is a major excitatory neurotransmitter in vertebrate central nervous system. L-glutamate enables synaptic transmission through ionotropic and metabotropic glutamate receptors. These receptors are indispensable in the brain. The main role of metabotropic glutamate receptors is to mediate slow excitatory and inhibitory responses by activation of intracellular messengers and to regulate cationic channels. Metabotropic glutamate receptors are involved in synaptic plasticity, different types of memory, learning, motoric coordination and neural development. On the other hand excitotoxicity of glutamate is often associated with neurodegenerative processes such as Alzheimer, Huntington and Parkinson disease. Metabotropic glutamate receptors are promising therapeutic targets for a treatment of psychiatric and neurological diseases. Targeted trafficking of metabotropic glutamate receptors to distinct parts of neurons is influenced by neuronal polarity and thus regulates sensing and transmission of extracellular signals. Newly detected heterodimeric receptors might be trafficked in a different way than homodimers and therefore our knowledge of molecular pathways of these complexes could help us with subsequent drug targeting. This work confirms heterodimerization of metabotropic glutamate receptor 1 into...
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