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Profilin

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Profilin
Profilin (blue) in complex withactin(green). (PDBcode:2BTF​)
Identifiers
SymbolProfilin
PfamPF00235
InterProIPR002097
SMARTPROF
PROSITEPS00414
SCOP22btf/SCOPe/SUPFAM
CDDcd00148
Available protein structures:
Pfam structures/ECOD
PDBRCSB PDB;PDBe;PDBj
PDBsumstructure summary
PDB2btf​

Profilinis anactin-binding proteininvolved in the dynamic turnover and reconstruction of theactincytoskeleton.[1]It is found in mosteukaryoticorganisms. Profilin is important for spatially and temporally controlled growth ofactinmicrofilaments, which is an essential process in cellular locomotion and cell shape changes. This restructuring of the actin cytoskeleton is essential for processes such asorgan development,wound healing,and the hunting down of infectious intruders by cells of theimmune system.

Profilin also binds sequences rich in theamino acidprolinein 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 thenucleussuch asmRNAsplicing.[2]

Profilin is the majorallergen(viaIgE) present inbirch,grass, and otherpollen.[citation needed]

Sources and distribution

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Profilins are proteins ofmolecular weightsof 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. Inmammaliancells, four profilinisoformshave been discovered; profilin-I is expressed in mosttissueswhile profilin-II is predominant inbrainandkidney.[3]

Asgard archaeause profilins.[4]Multiple eukaryoticdiatomspecies lack profilins.[5]

Profilin is essential to host cell invasion byToxoplasma gondii.Toxoplasmaprofilin is the specificpathogen-associated molecular pattern(PAMP) ofTLRs5, 11, and 12.[6]

Regulation of actin dynamics

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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-boundADPtoATPthereby 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 thelaw of mass action.[citation needed]
  • Profilin-actin complexes are fed into growing actin polymers by proteins such asformin,Wiskott-Aldrich syndrome proteinandVasodilator-stimulated phosphoproteinwhich 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.[citation needed]

Profilin binds some variants ofmembranephospholipids(phosphatidylinositol (4,5)-bisphosphateandinositol trisphosphate). The function of this interaction is the sequestration of profilin in an "inactive" form, from where it can be released by action of the enzymephospholipase C.[citation needed]

Profilin negatively regulatesPI(3,4)P2limiting recruitment oflamellipodiato the leading edge of the cell.[7]

Profilin is one of the most abundant actin monomer binders, but proteins such asCAPand (in mammals)thymosin β4have some functional overlaps with profilin. In contrast, ADF/cofilinhas some properties that antagonize profilin action.

History of discovery

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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.[8]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 apro-filamentousform), and release them upon a signal to make them accessible for fast actin polymer growth.

Allergen

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Profilin allergy is significantly associated with respiratory allergy to grass pollen (hay fever). After a person first becomes allergic to profilin through inhalation of grass or tree pollen, allergy to profilin-containing food and development ofpollen-food syndromeoccurs[9]: 3 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 toMercurialis annuawere profilin allergic.[9] 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.[9]As of 2018 there was no "solid therapeutic approach" to treat profilin allergy.[9]

As of 2018, the list of members of the profilin family identified as allergens contained:[9]

Human genes

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References

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  1. ^Gunning PW, Ghoshdastider U, Whitaker S, Popp D, Robinson RC (June 2015)."The evolution of compositionally and functionally distinct actin filaments".Journal of Cell Science.128(11): 2009–19.doi:10.1242/jcs.165563.PMID25788699.
  2. ^Di Nardo A, Gareus R, Kwiatkowski D, Witke W (November 2000)."Alternative splicing of the mouse profilin II gene generates functionally different profilin isoforms"(PDF).Journal of Cell Science.113(Pt 21): 3795–803.doi:10.1242/jcs.113.21.3795.PMID11034907.
  3. ^Witke W, Podtelejnikov AV, Di Nardo A, Sutherland JD, Gurniak CB, Dotti C, Mann M (February 1998)."In mouse brain profilin I and profilin II associate with regulators of the endocytic pathway and actin assembly".The EMBO Journal.17(4): 967–76.doi:10.1093/emboj/17.4.967.PMC1170446.PMID9463375.
  4. ^Akıl C, Robinson RC (October 2018). "Genomes of Asgard archaea encode profilins that regulate actin".Nature.562(7727): 439–443.Bibcode:2018Natur.562..439A.doi:10.1038/s41586-018-0548-6.PMID30283132.S2CID52917038.
  5. ^Aumeier, Charlotte; Polinski, Ellen; Menzel, Diedrik (October 2015)."Actin, actin-related proteins and profilin in diatoms: a comparative genomic analysis".Marine Genomics.23:133–142.doi:10.1016/j.margen.2015.07.002.ISSN1876-7478.PMID26298820.
  6. ^Salazar Gonzalez RM, Shehata H, O'Connell MJ, Yang Y, Moreno-Fernandez ME, Chougnet CA, Aliberti J (August 2014)."Toxoplasma gondii- derived profilin triggers human toll-like receptor 5-dependent cytokine production".Journal of Innate Immunity.6(5): 685–94.doi:10.1159/000362367.PMC4141014.PMID24861338.
  7. ^Bae YH, Ding Z, Das T, Wells A, Gertler F, Roy P (December 2010)."Profilin1 regulates PI(3,4)P2 and lamellipodin accumulation at the leading edge thus influencing motility of MDA-MB-231 cells".Proceedings of the National Academy of Sciences of the United States of America.107(50): 21547–52.Bibcode:2010PNAS..10721547B.doi:10.1073/pnas.1002309107.PMC3003040.PMID21115820.
  8. ^Carlsson L, Nyström LE, Sundkvist I, Markey F, Lindberg U (September 1977). "Actin polymerizability is influenced by profilin, a low molecular weight protein in non-muscle cells".Journal of Molecular Biology.115(3): 465–83.doi:10.1016/0022-2836(77)90166-8.PMID563468.
  9. ^abcdeRodríguez del Río, P; Díaz-Perales, A; Sánchez-García, S; Escudero, C; Ibáñez, Md; Méndez-Brea, P; Barber, D (2018-02-19)."Profilin, a Change in the Paradigm".Journal of Investigational Allergology and Clinical Immunology.28(1): 1–12.doi:10.18176/jiaci.0193.PMID28760720.

Further reading

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Bae YH, Ding Z, Das T, Wells A, Gertler F, Roy P (December 2010)."Profilin1 regulates PI(3,4)P2 and lamellipodin accumulation at the leading edge thus influencing motility of MDA-MB-231 cells".Proceedings of the National Academy of Sciences of the United States of America.107(50): 21547–52.Bibcode:2010PNAS..10721547B.doi:10.1073/pnas.1002309107.PMC3003040.PMID21115820.

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