Slit-Robo
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Slit-Robo
Slit-Robo is the name of a cell signaling protein complex with many diverse functions including axon guidance and angiogenesis. Slit (gene), Slit refers to a secreted protein that is most widely known as a repulsive axon guidance cue, and Roundabout (gene), Robo refers to its Cell surface receptor, transmembrane protein receptor. There are four different Robos and three Slits in vertebrates: ROBO1, Robo1, ROBO2, Robo2, ROBO3, Robo3/Rig-1, and ROBO4, Robo4, and SLIT1, Slit1, SLIT2, Slit2, SLIT3, Slit3. There are three Robos and a single Slit in ''Drosophila''. The corresponding Slit and Robo homologues in ''Caenorhabditis elegans, C. elegans'' are Slt and Sax-3, respectively. Slits are characterized by four distinct domains, each containing variable numbers of leucine-rich repeats (LRRs), seven to nine EGF-like domain, EGF repeats, an Laminin#Laminin G, ALPS domain (Agrin, Perlecan, Laminin, Slit), and a Cystine knot, cysteine knot. Robos are characterized by five Immunoglobulin ...
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Slit (gene)
Slit is a protein family, family of secreted extracellular matrix proteins which play an important signalling role in the neural development of most bilaterians (animals with bilateral symmetry). While lower animal species, including insects and nematode worms, possess a single Slit gene, humans, mice and other vertebrates possess three Slit homologs: SLIT1, Slit1, SLIT2, Slit2 and SLIT3, Slit3. Human ''Slits'' have been shown to be involved in certain pathological conditions, such as cancer and inflammation. The ventral midline of the central nervous system is a key place where axons can either decide to cross and laterally project or stay on the same side of the brain. The main function of Slit proteins is to act as midline repellents, preventing the crossing of longitudinal axons through the midline of the central nervous system of most bilaterian animal species, including mouse, mice, chickens, humans, insects, nematode worms and planarians. It also prevents the recrossing ...
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Roundabout (gene)
The Roundabout (Robo) family of proteins are single-pass transmembrane receptors that are highly conserved across many branches of the animal kingdom, from ''C. elegans'' to humans. They were first discovered in ''Drosophila'', through a mutant screen for genes involved in axon guidance. The ''Drosophila'' roundabout mutant was named after its phenotype, which resembled the circular traffic junctions (see roundabout). The Robo receptors are most well known for their role in the development of the nervous system, where they have been shown to respond to secreted Slit ligands. One well-studied example is the requirement for Slit-Robo signaling in regulation of axonal midline crossing. Slit-Robo signaling is also critical for many neurodevelopmental processes including formation of the olfactory tract, the optic nerve, and motor axon fasciculation. In addition, Slit-Robo signaling contributes to cell migration and the development of other tissues such as the lung, kidney, liv ...
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ROBO1
Roundabout homolog 1 is a protein that in humans is encoded by the ''ROBO1'' gene. Function Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range Chemotaxis, chemoattractants emanating from the midline. The protein encoded by ROBO1 is structurally similar to a Drosophila integral membrane protein which is encoded by the Drosophila roundabout gene (a member of the immunoglobulin gene superfamily) and is both an axon guidance receptor and a cell adhesion receptor, known to be involved in the decision by axons to cross the central nervous system midline. Two transcript variants encoding different Protein isoform, isoforms have been found for ROBO1. Clinical significance ''ROBO1'' was implicated in a communication disorder based on a Finland, Finnish pedigree with severe dyslexia. Analyses revealed a translocation had occurred ...
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Axon Guidance
Axon guidance (also called axon pathfinding) is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately is an area of ongoing research. Axon growth takes place from a region called the growth cone and reaching the axon target is accomplished with relatively few guidance molecules. Growth cone receptors respond to the guidance cues. Mechanisms Growing axons have a highly motile structure at the growing tip called the growth cone, which responds to signals in the extracellular environment that instruct the axon in which direction to grow. These signals, called guidance cues, can be fixed in place or diffusible; they can attract or repel axons. Growth cones contain receptors that recognize these guidance cues and interpret the signal into a chemotropic response. The general theoretical framework is that whe ...
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Cell Signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes. Signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical pressure, voltage, temperature, light, or chemical signals (e.g., small molecules, peptides, or gas). Cell signaling can occur over short or long distances, and as a result can be classified as autocrine, juxtacrine, intracrine, paracrine, or endocrine. Signaling molecules can be synthesized from various biosynthetic pathways and released through passive or active transports, or even from cell damage. Receptors play a key role in cell signaling as they are able to detect chemical signals or physical stimuli. Receptors are generally proteins located on the cell surface or within the interio ...
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Deleted In Colorectal Cancer
Netrin receptor DCC, also known as DCC, or colorectal cancer suppressor is a protein which in humans is encoded by the ''DCC'' gene. DCC has long been implicated in colorectal cancer and its previous name was ''Deleted in colorectal carcinoma''. Netrin receptor DCC is a single transmembrane receptor. Since it was first discovered in a colorectal cancer study in 1990, ''DCC'' has been the focus of a significant amount of research. ''DCC'' held a controversial place as a tumour suppressor gene for many years, and is well known as an axon guidance receptor that responds to netrin-1. More recently DCC has been characterized as a dependence receptor, and many hypotheses have been put forward that have revived interest in ''DCCs candidacy as a tumour suppressor gene, as it may be a ligand-dependent suppressor that is frequently epigenetically silenced. Background Early studies of colorectal tumours found that allelic deletions of segments of chromosome 18q occur in a very high perce ...
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Fibronectin Type III Domain
The Fibronectin type III domain is an evolutionarily conserved protein domain that is widely found in animal proteins. The fibronectin protein in which this domain was first identified contains 16 copies of this domain. The domain is about 100 amino acids long and possesses a beta sandwich structure. Of the three fibronectin-type domains, type III is the only one without disulfide bonding present. Fibronectin domains are found in a wide variety of extracellular proteins. They are widely distributed in animal species, but also found sporadically in yeast, plant and bacterial proteins. Human proteins containing this domain ABI3BP; ANKFN1; ASTN2; AXL; BOC; BZRAP1; C20orf75; CDON; CHL1; CMYA5; CNTFR; CNTN1; CNTN2; CNTN3; CNTN4; CNTN5; CNTN6; COL12A1; COL14A1; COL20A1; COL7A1; CRLF1; CRLF3; CSF2RB; CSF3R; DCC; DSCAM; DSCAML1; EBI3; EGFLAM; EPHA1; EPHA10; EPHA ...
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Tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Greek ''tyrós'', meaning ''cheese'', as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a Hydrophobe, hydrophobic amino acid, it is more hydrophilic than phenylalanine. It is Genetic code, encoded by the Genetic code#Codons, codons UAC and UAU in messenger RNA. Functions Aside from being a proteinogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes and functions as a receiver of phosphate groups that are transferred by way of protein kinases. Phosphorylation of the hyd ...
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Phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many enzymes. Glucose Phosphorylation of sugars is often the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by :D-glucose + ATP → D-glucose-6-phosphate + ADP : ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition) Hepatic cells are freely permeable to glucose, and ...
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Netrin
Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word "netr", which means "one who guides". Netrins are genetically conserved across nematode worms, fruit flies, frogs, mice, and humans. Structurally, netrin resembles the extracellular matrix protein laminin. Netrins are chemotropic; a growing axon will either move towards or away from a higher concentration of netrin. Though the detailed mechanism of axon guidance is not fully understood, it is known that netrin attraction is mediated through UNC-40/DCC cell surface receptors and repulsion is mediated through UNC-5 receptors. Netrins also act as growth factors, encouraging cell growth activities in target cells. Mice deficient in netrin fail to form the hippocampal comissure or the corpus callosum. A proposed model for netrin activity in the spinal column of developing human embryos is that netrins are released by the floor plate and then are picked up by receptor proteins embedded ...
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Co-receptor
A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell. Properties The term co-receptor is prominent in literature regarding signal transduction, the process by which external stimuli regulate internal cellular functioning.Gomperts, BD.; Kramer, IM. Tatham, PER. (2002). Signal transduction. Academic Press. ISBN. The key to optimal cellular functioning is maintained by possessing specific machinery that can carry out tasks efficiently and effectively. Specifically, the process through which intermolecular reactions forward and amplify extracellular signals across the cell surface has developed to occur by two mechanisms. First, cell surface receptors can directly transduce signals by possessing both serine and threonine or simply serine in the cytoplasmic domain. They can also transmit signals through adaptor m ...
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Ena/Vasp Homology Proteins
ENA/VASP homology proteins or EVH proteins are a family of closely related proteins involved in cell motility in vertebrate and invertebrate animals. EVH proteins are modular proteins that are involved in actin polymerization, as well as interactions with other proteins. Within the cell, Ena/VASP proteins are found at the leading edge of Lamellipodia and at the tips of filopodia. Ena, the founding member of the family was discovered in a drosophila genetic screen for mutations that act as dominant suppressors of the abl non receptor tyrosine kinase. Invertebrate animals have one Ena homologue, whereas mammals have three, named Mena, VASP, and Evl. Ena/VASP proteins promote the spatially regulated actin polymerization required for efficient chemotaxis in response to attractive and repulsive guidance cues. Mice lacking functional copies of all three family members display pleiotropic phenotypes including exencephaly, edema, failures in neurite formation, and embryonic lethality. ...
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