Profilin is an

actin-binding protein Actin-binding proteins (also known as ABPs) are proteins that bind to actin. This may mean ability to bind actin monomers, or polymers, or both. Many actin-binding proteins, including α-actinin, β-spectrin, dystrophin, utrophin and fimbrin, do t ...

involved in the dynamic turnover and reconstruction of the

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 ...

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 ...

. It is found in all

eukaryotic Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

organisms. Profilin is important for spatially and temporally controlled growth of

microfilaments, which is an essential process in cellular locomotion and cell shape changes. This restructuring of the actin cytoskeleton is essential for processes such as organ development,

wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...

, and the hunting down of infectious intruders by cells of the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

. Profilin also binds sequences rich in the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

in diverse proteins. While most profilin in the cell is bound to actin, profilins have over 50 different binding partners. Many of those are related to actin regulation, but profilin also seems to be involved in activities in the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucle ...

such as

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

splicing. Profilin is the major

allergen An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies. In technical terms ...

(via

IgE Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε c ...

) present in

birch A birch is a thin-leaved deciduous hardwood tree of the genus ''Betula'' (), in the family Betulaceae, which also includes alders, hazels, and hornbeams. It is closely related to the beech-oak family Fagaceae. The genus ''Betula'' contains 30 ...

, grass, and other

pollen Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametophyt ...

Sources and distribution

Profilins are proteins of

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

s of roughly 14–19 kDa. They are present as single genes in yeast, insects, and worms, and as multiple genes in many other organisms including plants. In

mammal Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...

ian cells, four profilin

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 discovered; profilin-I is expressed in most tissues while profilin-II is predominant in

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

and

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

. Asgard archaea use profilins. Profilin is essential to host cell invasion by ''

Toxoplasma gondii ''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...

''. ''Toxoplasma'' profilin is the specific

pathogen-associated molecular pattern Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. A vast arra ...

(PAMP) of TLRs 5, 11, and 12.

Regulation of actin dynamics

Profilin enhances actin growth in two ways: * Profilin binds to monomeric actin thereby occupying an actin-actin contact site; in effect, profilin sequesters actin from the pool of polymerizable actin monomers. However, profilin also catalyzes the exchange of actin-bound ADP to ATP thereby converting poorly polymerizing ADP-actin monomers into readily polymerizing ATP-actin monomers. On top of that, profilin has a higher affinity for ATP- than for ADP-actin monomers. Thus in a mixture of actin, profilin, and nucleotides (ADP and ATP), actin will polymerize to a certain extent, which may be estimated by the

law of mass action In chemistry, the law of mass action is the proposition that the rate of the chemical reaction is directly proportional to the product of the activities or concentrations of the reactants. It explains and predicts behaviors of solutions in dyna ...

. * Profilin-actin complexes are fed into growing actin polymers by proteins such as

formin Formins (formin homology proteins) are a group of proteins that are involved in the polymerization of actin and associate with the fast-growing end (barbed end) of actin filaments. Most formins are Rho-GTPase effector proteins. Formins regu ...

, Wiskott-Aldrich syndrome protein and

Vasodilator-stimulated phosphoprotein Vasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the ''VASP'' gene. Function Vasodilator-stimulated phosphoprotein (VASP) is a member of the Ena-VASP protein family. Ena-VASP family members contain an N-terminal ...

which contain proline-rich FH1-domains. This mode of stimulated actin polymerization is much faster than unaided polymerization. Profilin is essential for this mode of polymerization because it recruits the actin monomers to the proline-rich proteins. Profilin binds some variants of

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...

phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...

s (

phosphatidylinositol (4,5)-bisphosphate Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...

and

inositol trisphosphate Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the p ...

). The function of this interaction is the sequestration of profilin in an "inactive" form, from where it can be released by action of the enzyme

phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...

. Profilin negatively regulates PI(3,4)P₂ limiting recruitment of

lamellipodia The lamellipodium (plural lamellipodia) (from Latin ''lamella'', related to ', "thin sheet", and the Greek radical ''pod-'', "foot") is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional ...

to the leading edge of the cell. Profilin is one of the most abundant actin monomer binders, but proteins such as

CAP A cap is a flat headgear, usually with a visor. Caps have crowns that fit very close to the head. They made their first appearance as early as 3200 BC. Caps typically have a visor, or no brim at all. They are popular in casual and informal se ...

and (in mammals) thymosin β4 have some functional overlaps with profilin. In contrast, ADF/

cofilin ADF/cofilin is a family of actin-binding proteins associated with the rapid depolymerization of actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle contractio ...

has some properties that antagonize profilin action.

History of discovery

Profilin was first described by Lars Carlsson in the lab of Uno Lindberg and co-workers in the early 1970s as the first actin monomer binding protein. It followed the realization that not only muscle, but also non-muscle cells, contained high concentrations of actin, albeit in part in an unpolymerized form. Profilin was then believed to sequester actin monomers (keep them in a ''pro-filamentous'' form), and release them upon a signal to make them accessible for fast actin polymer growth.

Allergen

Profilin allergy is significantly associated with respiratory allergy to grass pollen (

hay fever Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, i ...

). After a person first becomes allergic to profilin through inhalation of grass or tree pollen, allergy to profilin-containing food and development of pollen-food syndrome occurs How often pollen-allergic people across Europe become profilin allergic varies widely; As of 1997, from about 5% of Swedish birch pollen–allergic people to 51% in Spanish people allergic to

Mercurialis annua ''Mercurialis annua'' is a species of flowering plant in the spurge family Euphorbiaceae known by the common name annual mercury or (rarely) French mercury. It is native to Europe, North Africa, and the Middle East but it is known on many other c ...

were profilin allergic. Profilin is the major allergen of certain food plants, for example, melon, orange, and soybean and thus allergy to melon, citrus fruits, tomato, and banana is a clinical marker of profilin hypersensitivity. As of 2018 there was no "solid therapeutic approach" to treat profilin allergy. As of 2018, the list of members of the profilin family identified as allergens contained: *

Actinidia deliciosa ''Actinidia deliciosa'', the fuzzy kiwifruit, is a fruiting vine native to Southern China. Other species of '' Actinidia'' are also found in China and range east to Japan and north into southern areas of Russian Far East. This species grows nat ...

(kiwi fruit) *

Ambrosia artemisiifolia ''Ambrosia artemisiifolia'', with the common names common ragweed, annual ragweed, and low ragweed, is a species of the genus '' Ambrosia'' native to regions of the Americas. Taxonomy The species name, ''artemisiifolia'', is given because the le ...

(short ragweed) *

Ananas comosus ''Ananas'' is a plant genus in the family Bromeliaceae. It is native to South America. The genus contains ''Ananas comosus'', the pineapple. Species The genus ''Ananas'' includes only two species: Gallery File:Pineapple.plantation.jpg, Pinea ...

(pineapple) *

Apium graveolens Celery (''Apium graveolens'') is a marshland plant in the family Apiaceae that has been cultivated as a vegetable since antiquity. Celery has a long fibrous stalk tapering into leaves. Depending on location and cultivar, either its stalks, lea ...

(celery) *

Arachis hypogaea The peanut (''Arachis hypogaea''), also known as the groundnut, goober (US), pindar (US) or monkey nut (UK), is a legume A legume () is a plant in the family Fabaceae (or Leguminosae), or the fruit or seed of such a plant. When used as ...

(peanut) *

Artemisia vulgaris ''Artemisia vulgaris'', the common mugwort, is a species of flowering plant in the daisy family Asteraceae. It is one of several species in the genus ''Artemisia'' commonly known as mugwort, although ''Artemisia vulgaris'' is the species most ...

(mugwort) *

Betula verrucosa ''Betula pendula'', commonly known as silver birch, warty birch, European white birch, or East Asian white birch, is a species of tree in the family Betulaceae, native to Europe and parts of Asia, though in southern Europe, it is only found a ...

(European white birch) and

Betula pendula ''Betula pendula'', commonly known as silver birch, warty birch, European white birch, or East Asian white birch, is a species of tree in the family Betulaceae, native to Europe and parts of Asia, though in southern Europe, it is only found a ...

(silver birch) *

Capsicum annuum ''Capsicum annuum'' is a species of the plant genus ''Capsicum'' native to southern North America, the Caribbean, and northern South America. This species is the most common and extensively cultivated of the five domesticated capsicums. The spec ...

(bell pepper) *

Chenopodium album ''Chenopodium album'' is a fast-growing weedy annual plant in the genus ''Chenopodium''. Though cultivated in some regions, the plant is elsewhere considered a weed. Common names include lamb's quarters, melde, goosefoot, wild spinach and fat-h ...

(pigweed) *

Citrus sinensis ''Citrus'' is a genus of flowering plant, flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as Orange (fruit), oranges, Lemon, lemons, grapefruits, pomelos, and lim ...

(sweet orange) *

Corylus avellana ''Corylus avellana'', the common hazel, is a species of flowering plant in the birch family Betulaceae. It is native to Europe and western Asia. It is an important component of the hedgerows that were the traditional field boundaries in lowland En ...

(hazel) *

Cucumis melo ''Cucumis melo'', also known as melon, is a species of ''Cucumis'' that has been developed into many cultivated varieties. The fruit is a pepo. The flesh is either sweet or bland, with or without a musky aroma, and the rind can be smooth (such as ...

(muskmelon) *

Daucus carota ''Daucus carota'', whose common names include wild carrot, European wild carrot, bird's nest, bishop's lace, and Queen Anne's lace (North America), is a flowering plant in the family Apiaceae. It is native to temperate regions of the Old Wor ...

(carrot) *

Glycine max Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

(soybean) *

Helianthus annuus The common sunflower (''Helianthus annuus'') is a large annual forb of the genus ''Helianthus'' grown as a crop for its edible oily seeds. Apart from cooking oil production, it is also used as livestock forage (as a meal or a silage plant), as b ...

(sunflower) *

Hevea brasiliensis ''Hevea brasiliensis'', the Pará rubber tree, ''sharinga'' tree, seringueira, or most commonly, rubber tree or rubber plant, is a flowering plant belonging to the spurge family Euphorbiaceae Euphorbiaceae, the spurge family, is a large fami ...

(para rubber tree

atex The ATEX directives are two EU directives describing the minimum safety requirements for workplaces and equipment used in explosive atmospheres. The name is an initialization of the French term ''Appareils destinés à être utilisés en ATmos ...

Malus domestica An apple is an edible fruit produced by an apple tree (''Malus domestica''). Apple trees are cultivated worldwide and are the most widely grown species in the genus ''Malus''. The tree originated in Central Asia, where its wild ancestor, ' ...

(apple) *

Olea europaea The olive, botanical name ''Olea europaea'', meaning 'European olive' in Latin, is a species of small tree or shrub in the family Oleaceae, found traditionally in the Mediterranean Basin. When in shrub form, it is known as ''Olea europaea'' ...

(olive) *

Phleum pratense Timothy (''Phleum pratense'') is an abundant perennial grass native to most of Europe except for the Mediterranean region. It is also known as timothy-grass, meadow cat's-tail or common cat's tail. It is a member of the genus ''Phleum'', consis ...

(timothy grass) *

Phoenix dactylifera ''Phoenix dactylifera'', commonly known as date or date palm, is a flowering plant species in the palm family, Arecaceae, cultivated for its edible sweet fruit called dates. The species is widely cultivated across northern Africa, the Middle Eas ...

(date palm) *

Prunus persica ''Prunus'' is a genus of trees and shrubs, which includes (among many others) the fruits plums, cherries, peaches, nectarines, apricots, and almonds. Native to the North American temperate regions, the neotropics of South America, and the paleo ...

(peach) *

Pyrus communis ''Pyrus communis'', the common pear, is a species of pear native plant, native to central and eastern Europe, and western Asia. It is one of the most important fruits of temperate regions, being the species from which most orchard pear cultivars ...

(pear) * Salsola kali (Russian thistle) *

Sinapis alba White mustard (''Sinapis alba'') is an annual plant of the family Brassicaceae. It is sometimes also referred to as ''Brassica alba'' or ''B. hirta''. Grown for its seeds, used to make the condiment mustard, as fodder crop, or as a green manure ...

(yellow mustard) *

Solanum lycopersicum The tomato is the edible berry of the plant ''Solanum lycopersicum'', commonly known as the tomato plant. The species originated in western South America, Mexico, and Central America. The Mexican Nahuatl word gave rise to the Spanish word ...

(tomato)

Human genes

PFN1 Profilin-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 reactio ...

PFN2 Profilin-2 is a protein that in humans is encoded by the ''PFN2'' gene. The protein encoded by this gene is a ubiquitous actin monomer-binding protein belonging to the profilin family. It is thought to regulate actin polymerization in response to ...

, PFN3, PFN4, PFN5

References

External links

* {{Cytoskeletal Proteins Proteins