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 ...
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 most
eukaryotic
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
organisms. Profilin is important for spatially and temporally controlled growth of
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 ...
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 systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
.
Profilin also binds sequences rich in the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
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 p ...
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
Nucleu ...
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 an otherwise harmless substance that triggers an allergic reaction in sensitive individuals by stimulating an immune response.
In technical terms, an allergen is an antigen that is capable of stimulating a type-I hypersensitivi ...
(via
IgE
Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isoform") 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 ...
) 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 3 ...
, grass, and other
pollen
Pollen is a powdery substance produced by most types of flowers of seed plants for the purpose of sexual reproduction. It consists of pollen grains (highly reduced Gametophyte#Heterospory, microgametophytes), which produce male gametes (sperm ...
.
Sources and distribution
Profilins are proteins of
molecular weight
A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...
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
A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...
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 and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...
have been discovered; profilin-I is expressed in most
tissues while profilin-II is predominant in
brain
The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...
and
kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
.
Asgard archaea use profilins. Multiple eukaryotic
diatom
A diatom (Neo-Latin ''diatoma'') is any member of a large group comprising several Genus, genera of algae, specifically microalgae, found in the oceans, waterways and soils of the world. Living diatoms make up a significant portion of Earth's B ...
species lack profilins.
Profilin is essential to host cell invasion by ''
Toxoplasma gondii
''Toxoplasma gondii'' () is a species of parasitic alveolate that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but members of the cat family (felidae) are the only known 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, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both p ...
(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 a chemical reaction is directly proportional to the product of the activities or concentrations of the reactants. It explains and predicts behaviors of solutions in dy ...
.
* Profilin-actin complexes are fed into growing actin polymers by proteins such as
formin,
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. Bi ...
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 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 ...
). 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 i ...
.
Profilin negatively regulates
PI(3,4)P2 limiting recruitment of
lamellipodia
The lamellipodium (: 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 act ...
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. The origin of the word "cap" comes from the Old French word "chapeau" which means "head co ...
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, actin microfilaments that give actin its characteristic dynamic instability. This dynamic instability is central to actin's role in muscle cont ...
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 rhinitis, inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a Allergy, type I hypersensitivity re ...
).
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 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 chinensis'' var. ''deliciosa'' (kiwifruit)
*
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 lea ...
(short ragweed)
*
Ananas comosus
The pineapple (''Ananas comosus'') is a tropical plant with an edible fruit; it is the most economically significant plant in the family Bromeliaceae.
The pineapple is indigenous to South America, where it has been cultivated for many centu ...
(pineapple)
*
Apium graveolens
''Apium graveolens'', known in English as wild celery,Streeter D, Hart-Davies C, Hardcastle A, Cole F, Harper L. 2009. ''Collins Flower Guide''. Harper Collins is an Old World species of flowering plant in the family Apiaceae. It was first desc ...
(celery)
*
Arachis hypogaea
The peanut (''Arachis hypogaea''), also known as the groundnut, goober (US), goober pea, pindar (US) or monkey nut (UK), is a legume crop grown mainly for its edible seeds. It is widely grown in the tropics and subtropics by small and large ...
(peanut)
*
Artemisia vulgaris
''Artemisia vulgaris'', commonly known as mugwort, common mugwort, or wormwood, 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 ''Art ...
(mugwort)
*
Betula verrucosa (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 (biology), family Betulaceae, native plant, native to Europe and parts of Asia, though in so ...
(silver birch)
*
Capsicum annuum
''Capsicum annuum'' is a fruiting plant from the family Solanaceae (nightshades), within the genus Capsicum which is native to the northern regions of South America and to southwestern North America. The plant produces Berry, berries of many color ...
(bell pepper)
*
Chenopodium album
''Chenopodium album'' is a fast-growing annual plant in the flowering plant family Amaranthaceae. Though cultivated in some regions, the plant is elsewhere considered a weed. Common names include lamb's quarters, melde, goosefoot, wild spinach a ...
(pigweed)
*
Citrus sinensis
''Citrus'' is a genus of flowering plant, flowering trees and shrubs in the family Rutaceae. Plants in the genus produce citrus fruits, including important crops such as Orange (fruit), oranges, Mandarin orange, mandarins, lemons, grapefruits, ...
(sweet orange)
*
Corylus avellana
''Corylus avellana'', the common hazel, is a species of flowering plant in the birch tree, birch family Betulaceae. The shrubs usually grow tall. The nut is round, in contrast to the longer Corylus maxima, filbert nut. Common hazel is native to E ...
(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 an aroma, and the rind can be smooth (such as ho ...
(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 World ...
(carrot)
*
Glycine max
The soybean, soy bean, or soya bean (''Glycine max'') is a species of legume native to East Asia, widely grown for its edible bean. Soy is a staple crop, the world's most grown legume, and an important animal feed.
Soy is a key source of f ...
(soybean)
*
Helianthus annuus
The common sunflower (''Helianthus annuus'') is a species of large annual forb of the daisy family Asteraceae. The common sunflower is harvested for its edible oily seeds, which are often eaten as a snack food. They are also used in the pro ...
(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, originally native to the Amazon basin, but is now p ...
(para rubber tree
atex
The ATEX directives are two of the EU directives describing the minimum safety requirements for workplaces and equipment used in explosive atmospheres. The name is an initialization of the term ''ATmosphères EXplosives'' ( French for "exp ...
*
Malus domestica
An apple is a round, edible fruit produced by an apple tree (''Malus'' spp.). Fruit trees of the orchard or domestic apple (''Malus domestica''), the most widely grown in the genus, are agriculture, cultivated worldwide. The tree originated ...
(apple)
*
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'', cons ...
(timothy grass)
*
Phoenix dactylifera
''Phoenix dactylifera'', commonly known as the date palm, is a flowering-plant species in the palm family Arecaceae, cultivated for its edible sweet #Fruits, fruit called dates. The species is widely cultivated across North Africa, northern A ...
(date palm)
*
Prunus persica
The peach (''Prunus persica'') is a deciduous tree first domesticated and cultivated in China. It bears edible juicy fruits with various characteristics, most called peaches and the glossy-skinned, non-fuzzy varieties called nectarines. Peach ...
(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''), also called yellow mustard, is an annual plant of the cabbage family. It is sometimes also referred to as ''Brassica alba'' or ''B. hirta''. It probably originated in the Mediterranean region, but is now ...
(yellow mustard)
*
Solanum lycopersicum
The tomato (, ), ''Solanum lycopersicum'', is a plant whose fruit is an edible berry that is eaten as a vegetable. The tomato is a member of the nightshade family that includes tobacco, potato, and chili peppers. It originated from and was d ...
(tomato)
Human genes
*
PFN1,
PFN2,
PFN3,
PFN4,
PFN5
References
Further reading
External links
*
{{Cytoskeletal Proteins
Proteins