Structure

Fimbrin belongs to the calponin

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 inhibition of the smooth muscle ATPase.- Sturcture and...

 homology

Homology (biology)

Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

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

Spectrin

Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure...

, dystrophin

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 costamere or the dystrophin-associated protein complex...

, ABP-120 and filamin

Filamin

Filamins are a class of proteins that hold two actin filaments at large angles.Types include:* FLNA* FLNB* FLNC...

, 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 and some signal transduction proteins to the actin cytoskeleton

Cytoskeleton

The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic 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).

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

Mesenchymal stem cell

Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts , chondrocytes and adipocytes...

 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).

Function

Fimbrin is present in several cell types, including intestinal microvilli, hair cell stereocilia

Stereocilia

In the inner ear, stereocilia are the mechanosensing organelles of hair cells, which respond to fluid motion in numerous types of animals for various functions, including hearing and balance. They are about 10–50 micrometers in length and share some similar features of microvilli...

 and fibroblast

Fibroblast

A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

 filopodia

Filopodia

Filopodia are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. They contain actin filaments cross-linked into bundles by actin-binding proteins, e.g. fascin and fimbrin. Filopodia form focal adhesions with the substratum, linking it to the...

 (2). 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

Morphogenesis , is the biological process that causes an organism to develop its shape...

 and endocytosis

Endocytosis

Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

 (1).

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

Cytokinesis is the process in which the cytoplasm of a single eukaryotic cell is divided to form two daughter cells. It usually initiates during the late stages of mitosis, and sometimes meiosis, splitting a binucleate cell in two, to ensure that chromosome number is maintained from one generation...

 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

Arabidopsis thaliana is a small flowering plant native to Europe, Asia, and northwestern Africa. A spring annual with a relatively short life cycle, arabidopsis is popular as a model organism in plant biology and genetics...

and Schizosaccharomyces pombe

Schizosaccharomyces pombe

Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast. It is used as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measure 3 to 4 micrometres in diameter and 7 to 14 micrometres in length...

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).