RAPGEF4
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RAPGEF4
Rap guanine nucleotide exchange factor (GEF) 4 (RAPGEF4), also known as exchange protein directly activated by cAMP 2 (EPAC2) is a protein that in humans is encoded by the ''RAPGEF4'' gene. Epac2 is a target of cAMP, a major second messenger in various cells. Epac2 is coded by the RAPGEF4 gene, and is expressed mainly in brain, neuroendocrine, and endocrine tissues. Epac2 functions as a guanine nucleotide exchange factor for the Ras-like small GTPase Rap upon cAMP stimulation. Epac2 is involved in a variety of cAMP-mediated cellular functions in endocrine and neuroendocrine cells and neurons. Gene and transcripts Human Epac2 is coded by RAPGEF4 located at chromosome 2q31-q32, and three isoforms (Epac2A, Epac2B, and Epac2C) are generated by alternate promoter usage and differential splicing. Epac2A (called Epac2 originally) is a multi-domain protein with 1,011 amino acids, and is expressed mainly in brain and neuroendocrine and endocrine tissues such as pancreatic islets and ne ...
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Cyclic AMP
Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway. History Earl Sutherland of Vanderbilt University won a Nobel Prize in Physiology or Medicine in 1971 "for his discoveries concerning the mechanisms of the action of hormones", especially epinephrine, via second messengers (such as cyclic adenosine monophosphate, cyclic AMP). Synthesis Cyclic AMP is synthesized from ATP by adenylate cyclase located on the inner side of the plasma membrane and anchored at various locations in the interior of the cell. Adenylate cyclase is ''activated'' by a range of signaling molecules through the activation of adenylate cyclase stimulatory G ( Gs)-protein-coupled receptors. Adenylate cyclase is ''inhibited'' by agonists of adenylat ...
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GLP-1
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage, which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 protein secondary structure includes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region. Alongside glucose-dependent insulinotropic peptide (GIP), GLP-1 is an incretin; thus, it has the ability to decrease blood sugar levels in a glucose-dependent manner by enhancing the secretion of insulin. Beside the insulinotropic effects, GLP-1 has been associated with numerous regulatory and protective ...
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Cyclic Nucleotide-binding Domain
Proteins that bind cyclic nucleotides (cAMP or cGMP) share a structural domain of about 120 residues. The best studied of these proteins is the prokaryotic catabolite gene activator (also known as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure. There are six invariant amino acids in this domain, three of which are glycine residues that are thought to be essential for maintenance of the structural integrity of the beta-barrel. cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. The cAPK's are composed of two different subunits, a catalytic chain and a regulatory chain, which contains both copies of the domain. The cGPK's are single chain enzymes that include the two copies of the domain in their N-terminal section. Vertebrate cyclic nucleotide-gated ion-channels also contain this domain ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Exocytosis
Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use of energy to transport material. Exocytosis and its counterpart, endocytosis, are used by all cells because most chemical substances important to them are large polar molecules that cannot pass through the hydrophobic portion of the cell membrane by passive means. Exocytosis is the process by which a large amount of molecules are released; thus it is a form of bulk transport. Exocytosis occurs via secretory portals at the cell plasma membrane called porosomes. Porosomes are permanent cup-shaped lipoprotein structure at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intra-vesicular contents from the cell. In exocytosis, membrane-bound secretory vesicles are carried to the cell membrane, where they ...
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Sarcoplasmic Reticulum
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other Cell (biology), cells. The main function of the SR is to store calcium ions (Ca2+). Calcium in biology, Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondrion, mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels a ...
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Diastolic
Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are re-filling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventricular diastole the relaxing of the ventricles. The term originates from the Greek word (''diastolē''), meaning "dilation", from (''diá'', "apart") + (''stéllein'', "to send"). Role in cardiac cycle A typical heart rate is 75 beats per minute (bpm), which means that the cardiac cycle that produces one heartbeat, lasts for less than one second. The cycle requires 0.3 sec in ventricular systole (contraction)—pumping blood to all body systems from the two ventricles; and 0.5 sec in diastole (dilation), re-filling the four chambers of the heart, for a total of 0.8 sec to complete the cycle. Early ventricular diastole During early ventricular diastole, pressure in the two ventricles begins to drop from the peak reached during systol ...
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Ca2+/calmodulin-dependent Protein Kinase II
/calmodulin-dependent protein kinase II (CaM kinase II or CaMKII) is a serine/threonine-specific protein kinase that is regulated by the /calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII is also necessary for homeostasis and reuptake in cardiomyocytes, chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation. Misregulation of CaMKII is linked to Alzheimer's disease, Angelman syndrome, and heart arrhythmia. Types There are two types of CaM kinase: * Specialized CaM kinases, such as the myosin light chain kinase that phosphorylates myosin, causing smooth muscles to contract * Multifunctional CaM kinases, also collectively called ''CaM kinase II'', which play a role in neurotransmitter secretion, transcription factor regulation, and glycogen metabolism. Structure, function, and autoregulation CaMKII accounts for 1–2% of all proteins in the brain, and ha ...
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Cardiac Arrhythmia
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia, and a resting heart rate that is too slow – below 60 beats per minute – is called bradycardia. Some types of arrhythmias have no symptoms. Symptoms, when present, may include palpitations or feeling a pause between heartbeats. In more serious cases, there may be lightheadedness, passing out, shortness of breath or chest pain. While most cases of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in sudden death. Arrhythmias are often categorized into four groups: extra beats, supraventricular tachycardias, ventricular arrhythmias and bradyarrhythmias. Extra beats include premature atrial contractions, premature ventricular contra ...
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β-adrenergic Receptor
The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like beta blockers, beta-2 (β2) agonists and alpha-2 (α2) agonists, which are used to treat high blood pressure and asthma, for example. Many cells have these receptors, and the binding of a catecholamine to the receptor will generally stimulate the sympathetic nervous system (SNS). The SNS is responsible for the fight-or-flight response, which is triggered by experiences such as exercise or fear-causing situations. This response dilates pupils, increases heart rate, mobilizes energy, and diverts blood flow from non-essential organs to skeletal muscle. These effects together tend to increase physical performance momentarily. History By the turn of the 19th century, it was agreed that the stimulation of sympathetic nerves could cause different ...
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Calyx Of Held
The Calyx of Held is a particularly large synapse in the mammalian Auditory system, auditory central nervous system, so named after Hans Held who first described it in his 1893 article ''Die centrale Gehörleitung''Held, H. "Die centrale Gehörleitung" Arch. Anat. Physiol. Anat. Abt, 1893 because of its resemblance to the sepal, calyx of a flower. Globular bushy cells in the anterior cochlear nucleus, anteroventral cochlear nucleus (AVCN) send axons to the contralateral medial nucleus of the trapezoid body (MNTB), where they synapse via these calyces on MNTB principal cells. These principal cells then project to the ipsilateral Superior olivary nucleus, lateral superior olive (LSO), where they inhibit postsynaptic neurons and provide a basis for Interaural level difference, interaural level detection (ILD), required for high frequency sound localization. This synapse has been described as the largest in the brain. The related endbulb of Held is also a large axon terminal smaller sy ...
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Synapse
In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from one neuron to another. Neurons are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the ''presynaptic'' neuron) comes into close apposition with the membrane of the target (''postsynaptic'') cell. Both the presynaptic and postsynaptic sites contain extensive arrays of molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an axon and the postsynaptic part is located on a dendrite or soma. Astrocytes also exchange information with the synaptic neurons, responding to synaptic activity and, in turn, regulating neurotransmission. Syna ...
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