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AMPAR
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic glutamate receptor ( iGluR) and predominantly sodium ion channel that mediates fast excitatory neurotransmission in the central nervous system (CNS). Its activation by the neurotransmitter glutamate facilitates rapid neuronal communication, essential for various brain functions, including learning and memory. Its name is derived from the ability to be activated by the artificial glutamate analog AMPA. The receptor was initially named the " quisqualate receptor" by Watkins and colleagues after the naturally occurring agonist quisqualate. Later, the receptor was designated as the "AMPA receptor" following the development of the selective agonist AMPA by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The ''GRIA2''-encoded AMPA receptor ligand binding core (GluA2 LBD) was the first glutamate receptor ion channel domain ...
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AMPA Receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic receptor, ionotropic glutamate receptor (iGluR) and predominantly sodium ion channel that mediates fast excitatory neurotransmission in the Central nervous system, central nervous system (CNS). Its activation by the neurotransmitter Glutamate (neurotransmitter), glutamate facilitates rapid neuronal communication, essential for various brain functions, including learning and memory. Its name is derived from the ability to be activated by the artificial glutamate analog AMPA. The receptor was initially named the "Quisqualic acid, quisqualate receptor" by Watkins and colleagues after the naturally occurring agonist quisqualic acid, quisqualate. Later, the receptor was designated as the "AMPA receptor" following the development of the selective agonist AMPA by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The ''GRIA2''- ...
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Glutamate Receptor-interacting Protein (GRIP)
Glutamate receptor-interacting protein (GRIP) refers to either a family of proteins that bind to the glutamate receptor or specifically to the GRIP1 (gene), GRIP1 protein within this family. Proteins in the glutamate receptor-interacting protein (GRIP) family have been shown to interact with GRIA2, GluR2, a common subunit in the AMPA receptor. This subunit also interacts with other proteins such as protein interacting with C-kinase1 (PICK1) and N-ethylmaleimide-sensitive fusion protein (N-ethylmaleimide sensitive fusion protein, NSF). Studies have begun to elucidate its function; however, much is still to be learned about these proteins. Discovery and history of GRIP 1 The discovery of the Glutamate Receptor Interacting Protein (GRIP-1) came as a result of the observation that Glutamate Receptors, such as the NMDA receptor, cluster at synapses. Shortly after this observation, researchers identified a region on the C-terminal region of NMDA receptors called the tSXV motif that has ...
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SAP97
Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a scaffold protein that in humans is encoded by the ''SAP97'' gene. SAP97 is a mammalian MAGUK-family member protein that is similar to the Drosophila protein Dlg1 (the protein is alternatively referred to as hDlg1, and the human gene is DLG1). SAP97 is expressed throughout the body in epithelial cells. In the brain it is involved in the trafficking of ionotropic receptors from the endoplasmic reticulum to the plasma membrane, and may be involved in the trafficking AMPAR during synaptic plasticity. Function SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain. There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane. SAP97's function has been investigated by reducing it ...
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Ionotropic Receptor
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter. When a presynaptic neuron is excited, it releases a neurotransmitter from vesicles into the synaptic cleft. The neurotransmitter then binds to receptors located on the postsynaptic neuron. If these receptors are ligand-gated ion channels, a resulting conformational change opens the ion channels, which leads to a flow of ions across the cell membrane. This, in turn, results in either a depolarization, for an excitatory receptor response, or a hyperpolarization, for an inhibitory response. These receptor proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain w ...
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AMPA
α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that .... There are several types of glutamatergic ion channels in the central nervous system including AMPA, kainic acid and ''N''-methyl-D-aspartic acid (NMDA) channels. In the synapse, these receptors serve very different purposes. AMPA can be used experimentally to distinguish the activity of one receptor from the other in order to understand their differing functions. AMPA generates fast excitatory postsynaptic potentials (EPSP). AMPA activates AMPA receptors that are non-selective cationic channels allowing the passage of Na+ an ...
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PDZ Domain
The PDZ domain is a common structural domain of 80-90 Amino acid, amino-acids found in the Signal transduction, signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to cytoskeletal components. Proteins with these domains help hold together and organize signaling complexes at cellular membranes. These domains play a key role in the formation and function of signal transduction complexes. PDZ domains also play a highly significant role in the anchoring of cell surface receptors (such as Cftr and FZD7) to the actin cytoskeleton via mediators like NHERF and ezrin. ''PDZ'' is an initialism combining the first letters of the first three proteins discovered to share the domain — DLG4, post synaptic density protein (PSD95), DLG1, Drosophila disc large tumor suppressor (Dlg1), and Tight junction protein 1, zonula occludens-1 protein (zo-1). PDZ domains have previously been referr ...
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Endoplasmic Reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little net". It is a type of organelle made up of two subunits – rough endoplasmic reticulum (RER), and smooth endoplasmic reticulum (SER). The endoplasmic reticulum is found in most eukaryotic cells and forms an interconnected network of flattened, membrane-enclosed sacs known as cisternae (in the RER), and tubular structures in the SER. The membranes of the ER are continuous with the outer nuclear membrane. The endoplasmic reticulum is not found in red blood cells, or spermatozoa. There are two types of ER that share many of the same proteins and engage in certain common activities such as the synthesis of certain lipids and cholesterol. Different types of Cell (biology), cells contain different ratios of the two types of ER dependin ...
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CACNG2
Calcium channel, voltage-dependent, gamma subunit 2, also known as CACNG2 or stargazin is a protein that in humans is encoded by the ''CACNG2'' gene. Function L-type calcium channels are composed of five subunits. The protein encoded by this gene represents one of these subunits, gamma, and is one of several gamma subunit proteins. It is an integral membrane protein that is thought to stabilize the calcium channel in an inactive (closed) state. This protein is similar to the mouse stargazin protein, mutations in which having been associated with absence seizures, also known as petit-mal or spike-wave seizures. This gene is a member of the neuronal calcium channel gamma subunit gene subfamily of the PMP-22/EMP/MP20 family. Stargazin is involved in the transportation of AMPA receptors to the synaptic membrane, and the regulation of their receptor rate constants — via its extracellular domain — once it is there. As it is highly expressed throughout the cerebral cortex, it i ...
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PSD-95
PSD-95 (postsynaptic density protein 95) also known as SAP-90 (synapse-associated protein 90) is a protein that in humans is encoded by the ''DLG4'' (discs large homolog 4) gene. PSD-95 is a member of the membrane-associated guanylate kinase (MAGUK) family. With PSD-93 it is recruited into the same NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. PSD-95 is the best studied member of the MAGUK-family of PDZ domain-containing proteins. Like all MAGUK-family proteins, its basic structure includes three PDZ domains, an SH3 domain, and a guanylate kinase-like domain (GK) connected by disordered linker regions. It is almost exclusively located in the post synaptic density of neurons, and is involved in anchoring synaptic proteins. Its direct and indirect binding partners include neuroligin, NMDA receptors, AMPA re ...
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PICK1
Protein Interacting with C Kinase - 1 is a protein that in humans is encoded by the ''PICK1'' gene. Function The protein encoded by this gene contains a PDZ domain, through which it interacts with protein kinase C, alpha ( PRKCA). This protein may function as an adaptor that binds to and organizes the subcellular localization of a variety of membrane proteins. It has been shown to interact with multiple glutamate receptor subtypes, monoamine plasma membrane transporters, as well as non-voltage gated sodium channels, and may target PRKCA to these membrane proteins and thus regulate their distribution and function. This protein has also been found to act as an anchoring protein that specifically targets PRKCA to mitochondria in a ligand-specific manner. Three transcript variants encoding the same protein have been found for this gene. Interactions PICK1 has been shown to interact with: * ACCN2, * BNC1, * Dopamine transporter, * GRIA2, * GRIA3, * GRIA4, * GRIK1, * ...
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GLUT1
Glucose transporter 1 (or GLUT1), also known as solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1), is a uniporter protein that in humans is encoded by the ''SLC2A1'' gene. GLUT1 facilitates the transport of glucose across the plasma membranes of mammalian cells. This gene encodes a facilitative glucose transporter that is highly expressed in erythrocytes and endothelial cells, including cells of the blood–brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. GLUT1 accounts for 2 percent of the protein in the plasma membrane of erythrocytes. During early development, GLUT1 expression is compartmentalized across different tissues, ensuring that metabolic requirements are met in a tissue-specific manner. This tissue-specific glucose metabolism is essential for regulating the differentiation of specific lineages, su ...
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Basic Helix–loop–helix
A basic helix–loop–helix (bHLH) is a protein structural motif that characterizes one of the largest families of dimerizing transcription factors. The word "basic" does not refer to complexity but to the chemistry of the motif because transcription factors in general contain basic amino acid residues in order to facilitate DNA binding. bHLH transcription factors are often important in development or cell activity. For one, BMAL1-Clock (also called ARNTL) is a core transcription complex in the molecular circadian clock. Other genes, like c-Myc and HIF-1, have been linked to cancer due to their effects on cell growth and metabolism. Structure The motif is characterized by two α-helices connected by a loop. In general, transcription factors (including this type) are dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding. In general, one helix is smaller, and due to the flexibility of this loop, allows dimerization by folding and pac ...
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