TALIN is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact[1] and, in lymphocytes, at cell–cell contacts. The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 9 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 15 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. [2][3] Talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and alpha-actinin. In mammalian cells vinculin is a membrane-cytoskeletal protein in Focal adhesion plaques that is involved in linkage of Integrin adhesion molecules to the [4] Integrin receptors are involved in the attachment of adherent cells to extracellular matrices[5][6] and of lymphocytes to other cells. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. A lymphocyte is a type of White blood cell in the Vertebrate Immune system. In these situations, talin codistributes with concentrations of integrins in the cell surface membrane. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. [7][8] Furthermore, in vitro binding studies suggest that integrins bind to talin, although with low affinity. In vitro ( Latin: within the glass refers to the technique of performing a given experiment in a controlled environment outside of a living Organism Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. [9] Talin also binds with high affinity to vinculin,[10] another cytoskeletal protein concentrated at points of cell adhesion. In mammalian cells vinculin is a membrane-cytoskeletal protein in Focal adhesion plaques that is involved in linkage of Integrin adhesion molecules to the cytoskeleton (also CSK is a cellular " Scaffolding " or " Skeleton " contained within the Cytoplasm. Cellular adhesion is the binding of a cell to another cell or to a Surface or matrix. [11] Finally, talin is a substrate for the Ca2+-activated protease, calpain II,[12] which is also concentrated at points of cell-substratum contact. A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link Calpains () are a family of Calcium -dependent non- lysosomal Cysteine Proteases ( Proteolytic Enzymes) expressed ubiquitously [13]
Talin Domains
Talin consists of a large C-terminal rod domain that contains bundles of α-alpha helices and an N-terminal FERM (band 4. The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal end, or A common motif in the Secondary structure of Proteins the alpha helix (α-helix is a right-handed coiled conformation resembling a spring, in which The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or 1, ezrin, radixin, and moesin) domain with three subdomains: F1, F2, and F3. [14][15][16][17] The F3 subdomain of the FERM domain contains the highest affinity integrin-binding site for integrin β tails and is sufficient to activate integrins. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. [18]
Model of Talin-Induced
Integrin Activation.
Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals.
Talin Activates Integrin αIIbβ3
A structure-function analysis reported recently[19] provides a cogent structural model (see top right) to explain talin-dependent integrin activation in three steps:
- ♦ (A) The talin F3 domain (surface representation; colored by charge), freed from its autoinhibitory interactions in the full-length protein, becomes available for binding to the integrin. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals.
- ♦ (B) F3 engages the membrane-distal part of the β3-integrin tail (in red), which becomes ordered, but the α-β integrin interactions that hold the integrin in the low-affinity conformation remain intact. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals. Integrins are Cell surface receptors that interact with the Extracellular matrix (ECM and mediate various intracellular signals.
- ♦ (C) In a subsequent step, F3 engages the membrane-proximal portion of the β3 tail while maintaining its membrane-distal interactions.
References
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- ^ Kupfer A, Singer SJ, Dennert G (1986). "On the mechanism of unidirectional killing in mixtures of two cytotoxic T lymphocytes. Unidirectional polarization of cytoplasmic organelles and the membrane-associated cytoskeleton in the effector cell". J. Exp. Med. 163 (3): 489–98. doi:10.1084/jem.163.3.489. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3081676.
- ^ Burn P, Kupfer A, Singer SJ (1988). "Dynamic membrane-cytoskeletal interactions: specific association of integrin and talin arises in vivo after phorbol ester treatment of peripheral blood lymphocytes". Proc. Natl. Acad. Sci. U. S. A. 85 (2): 497–501. doi:10.1073/pnas.85.2.497. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3124107.
- ^ Alan D. Michelson (2006). Platelets, Second Edition. Boston: Academic Press. ISBN 0-12-369367-5.
- ^ Hynes RO (1987). "Integrins: a family of cell surface receptors". Cell 48 (4): 549–54. doi:10.1016/0092-8674(87)90233-9. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3028640.
- ^ Ruoslahti E, Pierschbacher MD (1987). "New perspectives in cell adhesion: RGD and integrins". Science 238 (4826): 491–7. doi:10.1126/science.2821619. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 2821619.
- ^ Chen WT, Hasegawa E, Hasegawa T, Weinstock C, Yamada KM (1985). "Development of cell surface linkage complexes in cultured fibroblasts". J. Cell Biol. 100 (4): 1103–14. doi:10.1083/jcb.100.4.1103. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3884631.
- ^ Kupfer A, Singer SJ (1989). "The specific interaction of helper T cells and antigen-presenting B cells. IV. Membrane and cytoskeletal reorganizations in the bound T cell as a function of antigen dose". J. Exp. Med. 170 (5): 1697–713. doi:10.1084/jem.170.5.1697. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 2530300.
- ^ Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K (1986). "Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage". Nature 320 (6062): 531–3. doi:10.1038/320531a0. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 2938015.
- ^ Burridge K, Mangeat P (1984). "An interaction between vinculin and talin". Nature 308 (5961): 744–6. doi:10.1038/308744a0. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 6425696.
- ^ Geiger B (1979). "A 130K protein from chicken gizzard: its localization at the termini of microfilament bundles in cultured chicken cells". Cell 18 (1): 193–205. doi:10.1016/0092-8674(79)90368-4. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 574428.
- ^ Fox JE, Goll DE, Reynolds CC, Phillips DR (1985). "Identification of two proteins (actin-binding protein and P235) that are hydrolyzed by endogenous Ca2+-dependent protease during platelet aggregation". J. Biol. Chem. 260 (2): 1060–6. PMID 2981831.
- ^ Beckerle MC, Burridge K, DeMartino GN, Croall DE (1987). "Colocalization of calcium-dependent protease II and one of its substrates at sites of cell adhesion". Cell 51 (4): 569–77. doi:10.1016/0092-8674(87)90126-7. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 2824061.
- ^ Chishti AH, Kim AC, Marfatia SM, Lutchman M, Hanspal M, Jindal H, Liu SC, Low PS, Rouleau GA, Mohandas N, Chasis JA, Conboy JG, Gascard P, Takakuwa Y, Huang SC, Benz EJ, Bretscher A, Fehon RG, Gusella JF, Ramesh V, Solomon F, Marchesi VT, Tsukita S, Tsukita S, Hoover KB (1998). "The FERM domain: a unique module involved in the linkage of cytoplasmic proteins to the membrane". Trends Biochem. Sci. 23 (8): 281–2. doi:10.1016/S0968-0004(98)01237-7. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 9757824.
- ^ García-Alvarez B, de Pereda JM, Calderwood DA, Ulmer TS, Critchley D, Campbell ID, Ginsberg MH, Liddington RC (2003). "Structural determinants of integrin recognition by talin". Mol. Cell 11 (1): 49–58. doi:10.1016/S1097-2765(02)00823-7. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12535520.
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See also
External links
Actin-binding proteins (also known as ABP are proteins that bind to Actin. Merlin (also called Neurofibromin 2 or schwannomin) is a Cytoskeletal Protein. Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books
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