Fimbrin also known as is plastin 1 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the PLS1

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. Fimbrin is an

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

cross-linking protein important in the formation of

filopodia Filopodia (singular filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as ''microspikes'', and when they extend beyond the lame ...

Structure

Fimbrin belongs to the

calponin Calponin is a calcium binding protein. Calponin tonically inhibits the ATPase activity of myosin in smooth muscle. Phosphorylation of calponin by a protein kinase, which is dependent upon calcium binding to calmodulin, releases the calponin's ...

homology Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor * Sequence homology, biological homology between DNA, RNA, or protein sequences *Homologous chrom ...

(CH) domain superfamily of actin cross-linking proteins. Like other members of this superfamily, which include

α-actinin Actinin is a microfilament protein. Alpha-actinin-1 is necessary for the attachment of actin myofilaments to the Z-lines in skeletal muscle cells, and to the dense bodies in smooth muscle cells. The functional protein is an anti-parallel dimer, ...

, β-

spectrin Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane in eukaryotic cells. Spectrin forms pentagonal or hexagonal arrangements, forming a scaffold and playing an important role in maintenance of plasma membr ...

dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costa ...

, ABP-120 and

filamin Filamins are a class of proteins that hold two actin filaments at large angles. Filamin protein in mammals is made up of an actin-binding domain at its N-terminus that is followed by 24 immunoglobulin-like repeat modules of roughly 95 amino acids. ...

, it has a conserved 27 kDa 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 Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''. Intermedia ...

and some signal transduction proteins to the actin

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

. 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. In humans, three highly homologous, strictly tissue and locale specific

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ...

have been identified: I-, T- and L-fimbrin. L-fimbrin is found in only normal or transformed

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

where it becomes

phosphorylated 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, whi ...

in response to other factors such as

interleukin-1 The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. Discovery Discovery of these cytokines began with studies on t ...

. I-fimbrin is expressed by intestine and kidney epithelial cells. T-fimbrin is found in

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

and

mesenchymal Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood or bone. The interactions between mesenchyme and epithelium help to form nearly every o ...

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.

Function

Fimbrin is present in several distinct structures in different cell types, including intestinal

microvilli Microvilli (singular: microvillus) are microscopic cellular membrane protrusions that increase the surface area for diffusion and minimize any increase in volume, and are involved in a wide variety of functions, including absorption, secretion, ...

, hair cell

stereocilia Stereocilia (or stereovilli or villi) are non-motile apical cell modifications. They are distinct from cilia and microvilli, but are closely related to microvilli. They form single "finger-like" projections that may be branched, with normal cel ...

and

fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...

. It is usually associated with polarized actin filaments in membrane ruffles, filopodia, stereocilia and adhesion plaques. Sequence homology and biochemical properties show that fimbrin is highly conserved from yeast to humans. Yeast mutants lacking fimbrin are defective in

morphogenesis Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of devel ...

and

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. E ...

. Owing 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 Cytokinesis () is the part of the cell division process during which the cytoplasm of a single eukaryotic cell divides into two daughter cells. Cytoplasmic division begins during or after the late stages of nuclear division in mitosis and meios ...

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, there are fewer experimental data describing the overall domain organization of the molecule. Klein ''et al.'' (2004) detailed the crystal structure of the ''

Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...

'' and ''

Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically meas ...

'' 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.

Structure

Function

References

Further reading