Profilin

updated 29/4/02

A low molecular weight actin binding protein which seems to have been found in every eukaryotic species where it has been looked for.
The protein was identified after the discovery of a non-polymerised form of actin from Thyone sperm (Tilney ). This complex was found
to contain actin, and a 16kDa protein and was named "profilamentous actin" (Tilney, ) later abbreviated to "profilactin" (Tilney, 1976b).
However, although it is very likely that the 16 kDa protein is profilin, I do not believe that this has ever been shown. The name "profilin"
was coined by Carlson from the previous term "profilactin". The amino-acid sequence of the profilins are not very highly conserved
across the many phyla from those determined (protozoa, mammalian, yeast, insect, echinoderm, plant and even a virus), yet despite this
the structure is conserved (Schutt et al, 1993; Vinson et al, 1993; Federov et al, 1994; Federov et al, 1997). Possibly connected with the
sequence diversity, the ubiquity and abundance of profilins in eukaryotes is the fact that profilins are major allergens. Profilin has an
unusual property in its ability to bind poly-L-proline, and although the physiological significance of this accidental finding (Tanaka &
Shibata, 1985) is in itself very important, this has provided an easy way to purify the protein (Kaiser et al, 1989; Janmey, 1991). Profilin
binds to poly-L-proline as its actual function is to bind proline rich regions in a number of profilin binding proteins. Not only does
profilin bind a series of partners through the proline -rich binding domain but it also binds phosphatidylinositol 4, 5 bisphosphate (Lassing
& Lindberg, 1985). (This discovery was the first of a very long list of proteins that are now known to bind PIP2). The specificity of the
interaction has been determined by others (Machesky et al, 1992). The phosphoinositides dissociates the profilactin complex but the
situation is very much more interesting than this as profilin can shield PIP2 against hydrolysis by phospholipase C but not when the

lipase has been activated by phosphorylation (Goldschmidt-Clermont et al, 1991 ) bi and its low molecular weight ( about 15kd), profilin
retains its ability to bind:-actin, poly-proline, and phosphoinositides. This ability to bind phosphoinositides is most intriguing and it has
even been suggested to be the primary role of the protein in cells, since phosphoinositides provide a very important cell signalling
cascade, transducing messages from outside to inside the cell.
The role of profilin in actin polymerization.
Partly because of how it was first discovered and on its effects on the polymerization of pure actin, profilin has been described primarily
as an actin monomer sequestering protein. However, it is now appreciated that the role of profilin is much more subtle than being merely
an actin sequestering protein. In some situations profilin encourages the polymerization of actin onto the barbed ends of actin filaments.
Intracellular localisation of profilin.
In fibroblasts profilin has been found to be concentrated at the leading edge (Bu et al, 1992). Profilin is localised too to sites where PIP2
is enriched in plant hair cells (Braun et al, 1999), at the leading edge in the amoeba Acanthamoeba (Bubb et al, 1998)
The role of profilin in cytokinesis.
Profilin has been found to be necessary for complete cytokinesis in a number of organisms such as Schizosaccharomyces pombe
(Balasubramanian et al, 994), Saccharomyces cerevisiae (Chang et al, 1997), Dictyostelium discoidium (Haugwitz et al, 1994)

The self-association of profilin?

Some reports suggest that profilin can self-associate forming oligomers (Babich et al, 1996)

The role of profilin in formin-nucleated actin cable assembly[Edit]

Profilin binds simultaneously to formin and actin monomers; this interaction tethers multiple profilin-actin complexes near the
growing end of actin filaments, which promotes the processive addition of actin subunits [1, 2]. Profilin uses the energy from ATP
hydrolysis generated during actin polymerization to facilitate actin assembly [2]. Profilin binds to cytoplasmic ATP-actin monomers
better than cytoplasmic ADP-actin monomers [3].
Profilin has been suggested to generally increase the elongation rate of formin-associated filaments by:
* Catalyzing the exchange of ADP for ATP on actin monomers [4, 5].
* Blocking free monomers from elongating pointed ends [4].
* Lowering the critical concentration at the barbed end [2].
* Promoting the association of G-actin-ATP to the barbed end [6].
Importantly however, profilin also promotes disassembly of actin filaments by sequestering monomeric G-actin, thereby blocking its
association with the barbed ends and promoting its disassembly from the pointed ends of actin filaments [4]. The combined actions of
profilin and ADF/cofilin synergize to enhance turnover of actin filaments [7].

References

1. Watanabe N., Madaule P., Reid T., Ishizaki T., Watanabe G., Kakizuka A., Saito Y., Nakao K., Jockusch BM., Narumiya S.
p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for
profilin. EMBO J. 1997; 16(11). [PMID: 9214622]
2. Pantaloni D., Carlier MF. How profilin promotes actin filament assembly in the presence of thymosin beta 4. Cell 1993;
75(5). [PMID: 8252614]
3. Perelroizen I., Didry D., Christensen H., Chua NH., Carlier MF. Role of nucleotide exchange and hydrolysis in the function of
profilin in action assembly. J. Biol. Chem. 1996; 271(21). [PMID: 8647830]
4. Ressad F., Didry D., Egile C., Pantaloni D., Carlier MF. Control of actin filament length and turnover by actin depolymerizing
factor (ADF/cofilin) in the presence of capping proteins and ARP2/3 complex. J. Biol. Chem. 1999; 274(30). [PMID:
10409644]
5. Yarmola EG., Dranishnikov DA., Bubb MR. Effect of profilin on actin critical concentration: a theoretical analysis. Biophys.
J. 2008; 95(12). [PMID: 18835900]
6. Kang F., Purich DL., Southwick FS. Profilin promotes barbed-end actin filament assembly without lowering the critical
concentration. J. Biol. Chem. 1999; 274(52). [PMID: 10601251]
7. Didry D., Carlier MF., Pantaloni D. Synergy between actin depolymerizing factor/cofilin and profilin in increasing actin
filament turnover. J. Biol. Chem. 1998; 273(40). [PMID: 9748225]
Updated on: Mon, 20 Oct 2014 09:40:51 GMT
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