Caveolae
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Caveolae
In biology, caveolae (Latin for "little caves"; singular, caveola), which are a special type of lipid raft, are small (50–100 nanometer) invaginations of the plasma membrane in the cells of many vertebrates. They are the most abundant surface feature of many vertebrate cell types, especially endothelial cells, adipocytes and embryonic notochord cells. They were originally discovered by E. Yamada in 1955. These flask-shaped structures are rich in proteins as well as lipids such as cholesterol and sphingolipids and have several functions in signal transduction. They are also believed to play a role in mechanoprotection, mechanosensation, endocytosis, oncogenesis, and the uptake of pathogenic bacteria and certain viruses. Caveolins Formation and maintenance of caveolae was initially thought to be primarily due to caveolin, a 21 kD protein. There are three homologous genes of caveolin expressed in mammalian cells: Cav1, Cav2 and Cav3. These proteins have a common topology: ...
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Endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis (cell drinking) and phagocytosis (cell eating). It is a form of active transport. History The term was proposed by De Duve in 1963. Phagocytosis was discovered by Élie Metchnikoff in 1882. Pathways Endocytosis pathways can be subdivided into four categories: namely, receptor-mediated endocytosis (also known as clathrin-mediated endocytosis), caveolae, pinocytosis, and phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is .... *Clathrin-mediated endocytosis is mediated by the production of smal ...
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Pinocytosis
In cellular biology, pinocytosis, otherwise known as fluid endocytosis and bulk-phase pinocytosis, is a mode of endocytosis in which small molecules dissolved in extracellular fluid are brought into the cell through an invagination of the cell membrane, resulting in their containment within a small vesicle inside the cell. These pinocytotic vesicles then typically fuse with early endosomes to hydrolyze (break down) the particles. Pinocytosis is variably subdivided into categories depending on the molecular mechanism and the fate of the internalized molecules. Function In humans, this process occurs primarily for absorption of fat droplets. In endocytosis the cell plasma membrane extends and folds around desired extracellular material, forming a pouch that pinches off creating an internalized vesicle. The invaginated pinocytosis vesicles are much smaller than those generated by phagocytosis. The vesicles eventually fuse with the lysosome, whereupon the vesicle contents are digeste ...
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Lipid Raft
The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. It has been proposed that they are specialized membrane microdomains which compartmentalize cellular processes by serving as organising centers for the assembly of signaling molecules, allowing a closer interaction of protein receptors and their effectors to promote kinetically favorable interactions necessary for the signal transduction. Lipid rafts influence membrane fluidity and membrane protein trafficking, thereby regulating neurotransmission and receptor trafficking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but float freely within the membrane bilayer. Although more common in the cell membrane, lipid rafts have also been reported in other parts of the cell, such as the Golgi apparatus and lysosome ...
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Endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throug ...
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PTRF
Polymerase I and transcript release factor, also known as Cavin1, Cavin-1 or PTRF, is a protein which in humans is encoded by the ''PTRF'' gene. Function PTRF (Cavin1) has been shown to be crucial for caveola formation and function. Termination of RNA polymerase I catalyzed transcription is a 2-step process that involves pausing of transcription elongation and release of both the pre-ribosomal RNA and Pol I from the DNA template. The pausing is mediated by TTF1 and PTRF. PTRF is a soluble protein containing putative leucine zipper, nuclear localization signal, and PEST domains. Interactions PTRF (Cavin1) forms trimers with Cavin2 and Cavin3 in caveola formation and has been shown to interact with other membrane associating proteins such as EHD2 and caveolins. PTRF has been shown to interact with ZNF148 Zinc finger protein 148 is a protein that in humans is encoded by the ''ZNF148'' gene. Interactions ZNF148 has been shown to interact with PTRF and P53. See a ...
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Caveolin
In molecular biology, caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis. Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signaling molecules. They also induce positive (inward) membrane curvature by way of oligomerization, and hairpin insertion. Various classes of signaling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'. The caveolin gene family has three members in vertebrates: CAV1, CAV2, and CAV3, coding for the proteins caveolin-1, caveolin-2, and caveolin-3, respectively. All three members are membrane proteins with similar structure. Caveolin forms oligomers and associates with cholesterol and sphingolipids in certain areas of the cell membrane, leading to t ...
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Mechanosensation
Mechanosensation is the transduction of mechanical stimuli into neural signals. Mechanosensation provides the basis for the senses of light touch, hearing, proprioception, and pain. Mechanoreceptors found in the skin, called cutaneous mechanoreceptors, are responsible for the sense of touch. Tiny cells in the inner ear, called hair cells, are responsible for hearing and balance. States of neuropathic pain, such as hyperalgesia and allodynia, are also directly related to mechanosensation. A wide array of elements are involved in the process of mechanosensation, many of which are still not fully understood. Cutaneous mechanoreceptors Cutaneous mechanoreceptors are physiologically classified with respect to conduction velocity, which is directly related to the diameter and myelination of the axon. Rapidly adapting and slowly adapting mechanoreceptors Mechanoreceptors that possess a large diameter and high myelination are called ''low-threshold mechanoreceptors''. Fibers that respond ...
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Nystatin
Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat '' Candida'' infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin. Common side effects when applied to the skin include burning, itching, and a rash. Common side effects when taken by mouth include vomiting and diarrhea. During pregnancy use in the vagina is safe while other formulations have not been studied in this group. It works by disrupting the cell membrane of the fungal cells. Nystatin was discovered in 1950 by Rachel Fuller Brown and Elizabeth Lee Hazen. It was the first polyene macrolide antifungal. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. It is made from the bacterium '' Streptomyces noursei'' ...
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Genistein
Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen. It was first isolated in 1899 from the dyer's broom, ''Genista tinctoria''; hence, the chemical name. The compound structure was established in 1926, when it was found to be identical with that of prunetol. It was chemically synthesized in 1928. It has been shown to be the primary secondary metabolite of the ''Trifolium'' species and ''Glycine max L''. Natural occurrences Isoflavones such as genistein and daidzein are found in a number of plants including lupin, fava beans, soybeans, kudzu, and psoralea being the primary food source, also in the medicinal plants, '' Flemingia vestita'' and '' F. macrophylla'', and coffee. It can also be found in ''Maackia amurensis'' cell cultures. Biological effects Besides functioning as an antioxidant and anthelmintic, many isoflavones have been sh ...
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Filipin
Filipin is a mixture of chemical compounds first isolated by chemists at the Upjohn company in 1955 from the mycelium and culture filtrates of a previously unknown actinomycete, '' Streptomyces filipinensis''. It was discovered in a soil sample collected in the Philippine Islands, hence the name filipin. The isolate possessed potent antifungal activity. It was identified as a polyene macrolide based on its characteristic UV-Vis and IR spectra. Functions Although the polyene macrolide antibiotics exhibit potent antifungal activity, most are too toxic for therapeutic applications, with the exceptions of amphotericin B and nystatin A1. Unlike amphotericin B and nystatin A1 which form sterol-dependent ion channels, filipin is thought to be a simple membrane disrupter. Since filipin is highly fluorescent and binds specifically to cholesterol, it has found widespread use as a histochemical stain for cholesterol. This method of detecting cholesterol in cell membranes is used clin ...
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Clathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle, hence the protein's name, which is derived from the Latin ''clathrum'' meaning lattice. Coat-proteins, like clathrin, are used to build small vesicles in order to transport molecules within cells. The endocytosis and exocytosis of vesicles allows cells to communicate, to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. The endocytic pathway can be hijacked by viruses and other pathogens in order to gain entry to the cell during infection. Structure The clathrin triskelion is composed of three clathrin heavy chains inter ...
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SDPR
Cavin-2 or Serum deprivation-response protein (SDPR) is a protein that in humans is encoded by the ''SDPR'' gene. Cavin-2 is highly expressed in a variety of human endothelial cells. This gene encodes a calcium-independent phospholipid-binding protein whose expression increases in serum-starved cells. This protein has also been shown to be a substrate for protein kinase C (PKC) phosphorylation. Function Cavin-2 is required for blood vessel formation (angiogenesis) in humans and zebrafish and required also for the endothelial cell proliferation, migration and invasion in humans. Cavin-2 plays an important role in endothelial cell maintenance by regulating eNOS activity. Cavin-2 controls the generation of nitric oxide (NO) in human endothelial cells by controlling the activity and stability of the protein endothelial nitric-oxide synthase (eNOS). Secretion Cavin-2 is highly secreted from human endothelial cells (HUVEC), they are secreted through endothelial microparticles (E ...
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