Keith Burridge (born 1 July 1950) is a British researcher and Kenan distinguished Professor at the University of North Carolina at Chapel Hill. [1] [ self-published source? ] His research on focal adhesions includes the discovery of many adhesion proteins including vinculin, [2] [3] talin [4] [5] and paxillin, [6] [7] and ranks him in top 1% of the most cited scientist in the field of molecular biology and genetics. [1] Burridge has published more than 200 peer reviewed articles.
He was born in 1950 in Dorset, England. He obtained his undergraduate degree in 1971 from the University of Cambridge, and then completed his PhD in Dennis Bray's laboratory in the MRC Laboratory of Molecular Biology (LMB), also in Cambridge, in 1975. [1] Using biochemical techniques, he showed that at least two distinct types of myosin II exist in non-muscle cells and that some cells expressed both types. [8] [9]
He went as a postdoc to James D. Watson's laboratory at Cold Spring Harbor where he met Elias Lazarides. [1] [2] They decided to compile their work on α-actinin and showed that α-actinin is distributed periodically along stress fibers. [10] [11] They also noted that there was a concentration of α-actinin in plaques at the ends of stress fibers. [10] [12] Since these regions would several years later be named focal adhesions, α-actinin was the first protein found to be concentrated at these sites. [2] While developing a procedure to purify α-actinin from smooth muscle, Burridge co-purified another protein, vinculin, [2] [3] independently of Benny Geiger's discovery. [13]
In 1981 Burridge left Cold Spring Harbor Lab for a faculty position at the University of North Carolina at Chapel Hill, where he continued to work on focal adhesions. [1] He discovered talin (protein) [4] [5] as another focal adhesion protein and then, in collaboration with Rick Horwitz's laboratory, showed that talin (protein) bound to the cytoplasmic domains of integrins. [14] [15] He then discovered other focal adhesion components including paxillin [6] [7] and contributed to the discovery of zyxin [16] and palladin. [17] Since then his work has focused on the signaling pathways emanating from focal adhesions, including RhoA-mediated contractility [18] [19] [20] and tyrosine phosphorylation in response to adhesion. [21] [22] [23]
In parallel with his scientific career, Keith Burridge has written several plays of varying length. His 10-minute play "Chocolates for Mr. Wolfowitz" appeared in the Knutsford Little Theatre short play festival of 2008 in the UK. [24] "The Art of Deception", based on the true story of the art forger Han van Meegeren, won 2014 best new play by Playwrights First. [25] "The First Woman President" is a one-woman, one act play, that was premiered in the Midtown International Theatre Festival in New York City in 2016. [26] In the play Edith Wilson looks back to when she took over running the country while concealing from the public that her husband, President Woodrow Wilson, had suffered a stroke [27]
Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface.
In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane.
In cell biology, focal adhesions are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell. More precisely, focal adhesions are the sub-cellular structures that mediate the regulatory effects of a cell in response to ECM adhesion.
Podosomes are conical, actin-rich structures found as appendages on the outer surface of the plasma membrane of animal cells. Their size ranges from approximately 0.5 μm to 2.0 μm in diameter. While usually situated on the periphery of the cellular membrane, these unique structures display a polarized pattern of distribution in migrating cells, situating at the front border between the lamellipodium and lamellum. Their primary purpose is connected to cellular motility and invasion; therefore, they serve as both sites of attachment and degradation along the extracellular matrix. Many different specialized cells exhibit these dynamic structures such as invadopodia,, osteoclasts, vascular smooth muscle cells, endothelial cells, and certain immune cells such as macrophages and dendritic cells.
Paxillin is a protein that in humans is encoded by the PXN gene. Paxillin is expressed at focal adhesions of non-striated cells and at costameres of striated muscle cells, and it functions to adhere cells to the extracellular matrix. Mutations in PXN as well as abnormal expression of paxillin protein has been implicated in the progression of various cancers.
LIM domains are protein structural domains, composed of two contiguous zinc fingers, separated by a two-amino acid residue hydrophobic linker. The domain name is an acronym of the three genes in which it was first identified. LIM is a protein interaction domain that is involved in binding to many structurally and functionally diverse partners. The LIM domain appeared in eukaryotes sometime prior to the most recent common ancestor of plants, fungi, amoeba and animals. In animal cells, LIM domain-containing proteins often shuttle between the cell nucleus where they can regulate gene expression, and the cytoplasm where they are usually associated with actin cytoskeletal structures involved in connecting cells together and to the surrounding matrix, such as stress fibers, focal adhesions and adherens junctions.
Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.
Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, 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 α-actinin.
α-Catenin (alpha-catenin) functions as the primary protein link between cadherins and the actin cytoskeleton. It has been reported that the actin binding proteins vinculin and α-actinin can bind to alpha-catenin. It has been suggested that alpha-catenin does not bind with high affinity to both actin filaments and the E-cadherin-beta-catenin complex at the same time. It has been observed that when α-catenin is not in a molecular complex with β-catenin, it dimerizes and functions to regulate actin filament assembly, possibly by competing with Arp2/3 protein. α-Catenin exhibits significant protein dynamics. However, a protein complex including a cadherin, actin, β-catenin and α-catenin has not been isolated.
PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by the PTK2 gene. PTK2 is a focal adhesion-associated protein kinase involved in cellular adhesion and spreading processes. It has been shown that when FAK was blocked, breast cancer cells became less metastatic due to decreased mobility.
Transforming growth factor beta-1-induced transcript 1 protein is a protein that in humans is encoded by the TGFB1I1 gene. Often put together with and studied alongside TGFB1I1 is the mouse homologue HIC-5. As the name suggests, TGFB1I1 is an induced form of the larger family of TGFB1. Studies suggest TGFB1I1 plays a role in processes of cell growth, proliferation, migration, differentiation and senescence. TGFB1I1 is most localized at focal adhesion complexes of cells, although it may be found active in the cytosol, nucleus and cell membrane as well.
Alpha-actinin-3, also known as alpha-actinin skeletal muscle isoform 3 or F-actin cross-linking protein, is a protein that in humans is encoded by the ACTN3 gene located on chromosome 11. All people have two copies (alleles) of this gene.
Alpha-actinin-2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.
Zyxin is a protein that in humans is encoded by the ZYX gene.
Alpha-parvin is a protein that in humans is encoded by the PARVA gene.
Stress fibers are contractile actin bundles found in non-muscle cells. They are composed of actin (microfilaments) and non-muscle myosin II (NMMII), and also contain various crosslinking proteins, such as α-actinin, to form a highly regulated actomyosin structure within non-muscle cells. Stress fibers have been shown to play an important role in cellular contractility, providing force for a number of functions such as cell adhesion, migration and morphogenesis.
Talin-1 is a protein that in humans is encoded by the TLN1 gene. Talin-1 is ubiquitously expressed, and is localized to costamere structures in cardiac and skeletal muscle cells, and to focal adhesions in smooth muscle and non-muscle cells. Talin-1 functions to mediate cell-cell adhesion via the linkage of integrins to the actin cytoskeleton and in the activation of integrins. Altered expression of talin-1 has been observed in patients with heart failure, however no mutations in TLN1 have been linked with specific diseases.
In structural and cell biology, the focal adhesion targeting domain is a conserved protein domain that was first identified in focal adhesion kinase (FAK), also known as PTK2 protein tyrosine kinase 2 (PTK2).
Talin-2 is a protein in humans that is encoded by the TLN2 gene. It belongs to the talin protein family. This gene encodes a protein related to talin-1, a cytoskeletal protein that plays a significant role in the assembly of actin filaments. Talin-2 is expressed at high levels in cardiac muscle and functions to provide linkages between the extracellular matrix and actin cytoskeleton at costamere structures to transduce force laterally.
Nancy Hogg FMedSci is an immunologist who has made major contributions in the field of adhesion molecules, focusing on the integrins expressed by leukocytes. Hogg was elected to the Academy of Medical Sciences in 2002 and currently holds an emeritus position at the Francis Crick Institute, London.
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