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Profilin

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

Profilin is an actin-binding protein involved in the dynamic turnover and reconstruction of the actin cytoskeleton.[1] It is found in most eukaryotic organisms. Profilin is important for spatially and temporally controlled growth of actin 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, and the hunting down of infectious intruders by cells of the immune system.

Profilin also binds sequences rich in the amino acid proline 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 such as mRNA splicing.[2]

Profilin is the major allergen (via IgE) present in birch, grass, and other pollen.[citation needed]

Sources and distribution

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Profilins are proteins of molecular weights 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 mammalian cells, four profilin isoforms have been discovered; profilin-I is expressed in most tissues while profilin-II is predominant in brain and kidney.[3]

Asgard archaea use profilins.[4] Multiple eukaryotic diatom species lack profilins.[5]

Profilin is essential to host cell invasion by Toxoplasma gondii. Toxoplasma profilin is the specific pathogen-associated molecular pattern (PAMP) of TLRs 5, 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-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.[citation needed]
  • Profilin-actin complexes are fed into growing actin polymers by proteins such as formin, Wiskott-Aldrich syndrome protein and Vasodilator-stimulated phosphoprotein 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.[citation needed]

Profilin binds some variants of membrane phospholipids (phosphatidylinositol (4,5)-bisphosphate and inositol 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 enzyme phospholipase C.[citation needed]

Profilin negatively regulates PI(3,4)P2 limiting recruitment of lamellipodia to the leading edge of the cell.[7]

Profilin is one of the most abundant actin monomer binders, but proteins such as CAP and (in mammals) thymosin β4 have some functional overlaps with profilin. In contrast, ADF/cofilin has 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 a pro-filamentous form), 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 of pollen-food syndrome occurs [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 to Mercurialis annua were 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. PMID 25788699.
  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. PMID 11034907.
  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. PMC 1170446. PMID 9463375.
  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. PMID 30283132. S2CID 52917038.
  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. ISSN 1876-7478. PMID 26298820.
  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. PMC 4141014. PMID 24861338.
  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. PMC 3003040. PMID 21115820.
  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. PMID 563468.
  9. ^ a b c d e Rodríguez 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. PMID 28760720.

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. PMC 3003040. PMID 21115820.

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