Profilin: emerging concepts and lingering misconceptions

Yarmola, Elena G.; Bubb, Michael R.

doi:10.1016/j.tibs.2006.02.006

Cited by 92 publications

(88 citation statements)

References 53 publications

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“…We note that this relation holds only for ADP-actin since it assembles following a reversible equilibrium reaction, and therefore C c reflects the (average) affinity of ADP-actin monomers for filament ends. Assembly of ATP-actin, on the other hand, has additional linked equilibria (e.g., ATP hydrolysis and P i release), and the barbed and pointed filament ends vary in nucleotide composition (21,22). The C c of ATP-actin monomers is therefore more accurately described as the monomer concentration once polymerization has reached steady-state.…”

Section: Resultsmentioning

confidence: 99%

Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness

Kang

Bradley

McCullough

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

148

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The assembly of actin monomers into filaments and networks plays vital roles throughout eukaryotic biology, including intracellular transport, cell motility, cell division, determining cellular shape, and providing cells with mechanical strength. The regulation of actin assembly and modulation of filament mechanical properties are critical for proper actin function. It is well established that physiological salt concentrations promote actin assembly and alter the overall bending mechanics of assembled filaments and networks. However, the molecular origins of these salt-dependent effects, particularly if they involve nonspecific ionic strength effects or specific ion-binding interactions, are unknown. Here, we demonstrate that specific cation binding at two discrete sites situated between adjacent subunits along the long-pitch helix drive actin polymerization and determine the filament bending rigidity. We classify the two sites as "polymerization" and "stiffness" sites based on the effects that mutations at the sites have on salt-dependent filament assembly and bending mechanics, respectively. These results establish the existence and location of the cation-binding sites that confer salt dependence to the assembly and mechanics of actin filaments.ion-linkage | structural bioinformatics | persistence length | polyelectrolyte T he polymerization of the protein actin into double-stranded helical filaments powers many eukaryotic cell movements and provides cells with mechanical strength and integrity (1-4). Filament formation is favored when the total actin concentration exceeds the critical concentration (C c ) for assembly-defined as the monomer concentration at steady state for ATP-actin, or the dissociation constant for the reversible-equilibrium binding reaction of monomer binding to ADP-actin filament ends. Accordingly, the C c of ADP-actin is linked to the filament subunit interaction free energy such that lower C c values reflect greater thermodynamic stability (5).The effects of solution ionic conditions on the assembly and stability of actin filaments have been investigated for several decades (6-12). The actin C c and (monomer and filament) conformation depend on the nucleotide-associated divalent cation (Ca 2þ or Mg 2þ ) as well as the type and concentration of ions in solution (6, 7, 13-15), a behavior shared among characterized actins and their bacterial homologs (16). However, it is not firmly established if these salt effects on actin filament assembly and mechanics originate from nonspecific ion effects (e.g., electrostatic screening, counterion condensation, etc.) and/or specific ion binding interactions, potentially at discrete sites. Identification of saturable cation binding sites with different affinities favors specific and discrete binding sites on monomers (8-10, 17), but the location of these sites and their contributions to filament assembly and stiffness are unknown.Here we identify distinct cation-binding sites at subunit interfaces that regulate actin filament assembly and rigidity. Sit...

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Section: Resultsmentioning

confidence: 99%

Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness

Kang

Bradley

McCullough

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

148

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“…Profilin binds to poly-(L-proline) (PLP) with high affinity (19)(20)(21), a property that is exploited in the purification of many profilins (16)(17)(18). The amino acid sequence of profilins is not very highly conserved across many phyla (protozoa, mammalian, yeast, insect, echinoderm and plant); despite this, the structure is conserved (22,23). Possibly connected with the sequence diversity, ubiquity, and abundance of profilins in eukaryotes is the fact that plant profilins are important cross-reactive allergens, and are identified as pan-allergens (23).…”

Section: Allergic Subjects and Case Historymentioning

confidence: 99%

Skin prick test analysis reveals cross-sensitization to tomato profilin and grass pollen in nasobronchialallergic patients with history of tomato food allergy

Hegde

Modesti²,

Venkatesh

2018

Eur Ann Allergy Clin Immunol

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SummaryThe association between grass pollen sensitization and food allergy to tomato is of great interest. We report here, the first such study in Indian population. We investigated 246 allergic rhinitis / asthma patients by diagnostic case history and skin prick test (SPT); grass pollen mix, tomato extract and purified tomato profilin were used for SPT. Tomato profilin was purified by affinity chromatography, and analyzed by HPLC (95% purity) and SDS-PAGE (14 kDa).We observed that 38% of the patients had sensitization to both grass pollen and tomato fruit, of which 92% were sensitized to tomato profilin. Among patients with a history of food allergy to tomato fruit, the association was more pronounced (66%). Tomato profilin appears to be an important cross-sensitizing panallergen in respiratory allergic patients in the Indian subcontinent.

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“…This helps ensure that newly polymerized actin filaments are oriented in the direction of cell migration with their barbed ends directed towards the plasma membrane. The rate of polymerization at barbed ends is also modulated by capping proteins [10], which stearically hinder monomer addition, and by the availability of monomers that are usually maintained in complexes with profilin or thymosin, which are permissive for polymerization but prevent inappropriate polymerization [11]. The activity of the polymerization machinery is very tightly regulated.…”

mentioning

confidence: 99%

The actin cytoskeleton in cancer cell motility

Olson

Sahai

2008

Clin Exp Metastasis

483

392

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Cancer cell metastasis is a multi-stage process involving invasion into surrounding tissue, intravasation, transit in the blood or lymph, extravasation, and growth at a new site. Many of these steps require cell motility, which is driven by cycles of actin polymerization, cell adhesion and acto-myosin contraction. These processes have been studied in cancer cells in vitro for many years, often with seemingly contradictory results. The challenge now is to understand how the multitude of in vitro observations relates to the movement of cancer cells in living tumour tissue. In this review we will concentrate on actin protrusion and acto-myosin contraction. We will begin by presenting some general principles summarizing the widely-accepted mechanisms for the co-ordinated regulation of actin polymerization and contraction. We will then discuss more recent studies that investigate how experimental manipulation of actin dynamics affects cancer cell invasion in complex environments and in vivo.

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Profilin: emerging concepts and lingering misconceptions

Cited by 92 publications

References 53 publications

Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness

Identification of cation-binding sites on actin that drive polymerization and modulate bending stiffness

Skin prick test analysis reveals cross-sensitization to tomato profilin and grass pollen in nasobronchialallergic patients with history of tomato food allergy

The actin cytoskeleton in cancer cell motility

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