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Fimbrin is an actin cross-linking protein. To understand actin cross-linking in context, one must first understand the function of actin itself within the cell. The actin monomer, known as G-actin, is a globular protein that polymerizes helically to form F-actin microfilaments, the smallest of the three main components of the cytoskeleton. Along with intermediate filaments and microtubules, microfilaments comprise the three-dimensional structural support network inside the eukaryotic cell. Actin filaments are involved in cell motility, cell-substrate interactions, transport processes, cytokinesis, and the establishment and maintenance of cell morphology (3). A highly conserved protein, actin differs by no more than 5% among species as diverse as algae and humans.
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The superfamily of actin cross-linking proteins facilitates organization of the actin cytoskeleton via bundling and networking of actin filaments. Bundles and networks combine to provide a three-dimensional network that supports the plasma membrane and mediates cell shape. In bundles, the actin filaments are densely packaged in parallel arrays. In networks, however, the actin filaments criss-cross in a relatively loose formation. This criss-crossing often occurs at right angles forming a grid-like network. When associated with the plasma membrane, actin filament networks are two-dimensional, much like a web or a net. Alternatively, three-dimensional networks provide support within the cell and grant the cytosol its gel-like properties. The actin filaments involved in all bundles and networks are held together by actin cross-linking proteins, such as fimbrin, that logically contain two actin-binding sites (4).
Fimbrin belongs to the calponin homology (CH) domain superfamily of actin cross-linking proteins. Other members of this superfamily include alpha-actinin, beta-spectrin, dystrophin, ABP-120, and filamin. These proteins share a conserved 27-kD actin-binding domain that contains a tandem duplication of a sequence that is homologous to calponin. In addition to cross-linking actin filaments into bundles and networks, CH domains also bind intermediate filaments and some signal transduction proteins to the actin cytoskeleton. Structural comparison of actin filaments and fimbrin CH domain-decorated actin filaments has revealed changes in the actin structure due to fimbrin mediated cross-linking that may affect the actin filaments’ affinity for other actin-binding proteins and may be part of the regulation of the cytoskeleton itself (1).
Fimbrin is present in a variety of places including intestinal microvilli, hair cell stereocilia, and fibroblast filopodia (2). It is usually associated with polarized actin filaments in membrane ruffles, filopodia, stereocilia, and adhesion plaques. In humans, three highly homologous, strictly tissue and locale specific isoforms have been identified: I-, T-, and L-fimbrin (1). L-fimbrin is found in only normal or transformed leukocytes where it becomes phosphorylated in response to other factors such as interleukin-1. T-fimbrin, on the other hand, is found in epithelial and mesenchymal cells derived from solid tissue where it does not become phosphorylated. Differences in expression, sequence, and phosphorylation among the various fimbrin isoforms suggest the likelihood of functional differences (2). Highlighting the importance of fimbrin’s role in the cell, sequence homology and biochemical properties show that fimbrin is highly conserved from yeast to humans. Yeast mutants lacking fimbrin are defective in morphogenesis and endocytosis (1).
Due to the close proximity of its tandem actin-binding domains, fimbrin directs the formation of tightly bundled actin filaments that participate in dynamic processes, including cytokinesis in yeast and host cell invasion by enteropathic bacteria. Although fimbrin’s involvement in processes like these as well as its role in assembly and regulation of microfilament networks are well documented, experimental data describing the overall domain organization of the molecule is just beginning to emerge. Klein et al. published a paper in 2004 that detailed for the first time the crystal structure of the Arabidopsis thaliana and Schizosaccharomyces pombe fimbrin cores in an attempt to highlight the compact and distinctly asymmetric organization of the fimbrin molecule. This structural study of the fimbrin core represents the first detailed structural description of a functional actin cross-linking protein (3).
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Fimbrin". A list of authors is available in Wikipedia.|