Gelsolin, a Multifunctional Actin Regulatory Protein

polyphosphoinositide 4,5-bisphosphate phosphatidylinositol 5-kinase The actin cytoskeleton is an essential scaffold for integrating membrane and intracellular functions. It is very dynamic and is remodeled in response to a variety of signals. Growth factor stimulation promotes actin assembly at the plasma membrane to generate movement, whereas apoptotic signals cause cytoskeletal destruction to elicit characteristic membrane blebbing and morphological changes. Gelsolin is a Ca2+- and polyphosphoinositide 4,5-bisphosphate (PIP2)1-regulated actin filament severing and capping protein that is implicated in actin remodeling in growing and in apoptotic cells (reviewed in Refs. 1Liu Y.T. Rozelle A.L. Yin H.L. Maruta H. Kohama K. G Proteins, Cytoskeleton and Cancer. R. G. Landes Company, Austin, TX1998: 19-35Google Scholar and2Kwiatkowski D.J. Curr. Opin. Cell Biol. 1999; 11: 103-108Crossref PubMed Scopus (326) Google Scholar). This review summarizes data supporting the role of gelsolin in cytoskeletal remodeling and phosphoinositide signaling and discusses the structural basis for the Ca2+ and PIP2regulation of severing and capping by gelsolin. Gelsolin is the most potent actin filament severing protein identified to date. Severing is the weakening of enough non-covalent bonds between actin molecules within a filament to break the filament in two. Gelsolin severs stoichiometrically and with close to 100% efficiency (3Selden L.A. Kinosian H.J. Newman J. Lincoln B. Hurwitz C. Gershman L.C. Estes J.E. Biophys. J. 1998; 75: 3101-3109Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar). Severing is initiated after gelsolin binds to the side of an actin filament. Gelsolin binds filaments rapidly but severs slowly (3Selden L.A. Kinosian H.J. Newman J. Lincoln B. Hurwitz C. Gershman L.C. Estes J.E. Biophys. J. 1998; 75: 3101-3109Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar); the delay may reflect the time required for structural rearrangement within gelsolin (see “Structural Basis for Ca2+ Regulation”) and in the filament (4McGough A. Chiu W. Way M. Biophys. J. 1998; 74: 764-772Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar) prior to severing. Gelsolin changes actin conformation and kinks the actin filament (4McGough A. Chiu W. Way M. Biophys. J. 1998; 74: 764-772Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar), suggesting a mechanical basis for severing. After severing, gelsolin remains attached to the barbed end of the filament as a cap. As a result, short actin filaments that cannot reanneal with each other or elongate at their barbed ends are generated. In this way, the actin network is disassembled. The importance of Ca2+-mediated actin severing has been clearly documented during platelet activation (5Hartwig J.H. J. Cell Biol. 1992; 118: 1421-1442Crossref PubMed Scopus (336) Google Scholar), and gelsolin is the only known Ca2+-dependent severing protein identified to date. Gelsolin severing can also have a constructive effect because it increases the number of filaments. Uncapping of gelsolin from these filaments generates many polymerization-competent ends from which actin can grow to rebuild the cytoskeleton to new specifications. Therefore, gelsolin can promote actin polymerization by severing followed by uncapping (mechanism B, as discussed in the Prologue (74Yin H.L. Stull J.T. J. Biol. Chem. 1999; 274: 32529-32530Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar) of this series). Cells from gelsolin null mice exhibit a variety of motility and actin defects. Gelsolin null fibroblasts have pronounced actin stress fibers (6Witke W. Sharpe A.H. Hartwig J.H. Azuma T. Stossel T.P. Kwiatkowski D.J. Cell. 1995; 81: 41-51Abstract Full Text PDF PubMed Scopus (379) Google Scholar), and this phenotype is consistent with an inability to sever and remodel actin filaments. They do not ruffle in response to growth factor (7Azuma T. Witke W. Stossel T.P. Hartwig J.H. Kwiatkowski D.J. EMBO J. 1998; 17: 1362-1370Crossref PubMed Scopus (235) Google Scholar), and they exhibit defective chemotaxis and wound healing. The rate of clotting is reduced (6Witke W. Sharpe A.H. Hartwig J.H. Azuma T. Stossel T.P. Kwiatkowski D.J. Cell. 1995; 81: 41-51Abstract Full Text PDF PubMed Scopus (379) Google Scholar), as would be consistent with the requirement of actin severing for platelet activation (5Hartwig J.H. J. Cell Biol. 1992; 118: 1421-1442Crossref PubMed Scopus (336) Google Scholar). Neurite retraction is defective (8Lu M. Witke W. Kwiatkowski D.J. Kosik K.S. J. Cell Biol. 1997; 138: 1279-1287Crossref PubMed Scopus (118) Google Scholar), and neurons are more susceptible to glutamate-induced excito-toxicity (9Endres M. Fink K. Zhu J. Stagliano N.E. Bondala V. Geddes J.W. Azuma T. Mattson M.P. Kwiatkowski D.J. Moscowitz M.A. J. Clin. Invest. 1999; 10: 161-178Google Scholar). Neutrophil extravasation is compromised (6Witke W. Sharpe A.H. Hartwig J.H. Azuma T. Stossel T.P. Kwiatkowski D.J. Cell. 1995; 81: 41-51Abstract Full Text PDF PubMed Scopus (379) Google Scholar). These findings establish the importance of gelsolin in maintaining motility and actin dynamics. Despite multiple cellular pathology, the null animals (in a mixed strain background) are without gross phenotypic defects. This may reflect the existence of potent compensatory mechanisms. However, the compensation is incomplete and varies with the genetic background of the knockout animals. Gelsolin null animals in a pure strain mouse background are non-viable at perinatal and early postnatal stages (2Kwiatkowski D.J. Curr. Opin. Cell Biol. 1999; 11: 103-108Crossref PubMed Scopus (326) Google Scholar), indicating that gelsolin is necessary for survival. Membrane ruffling is a functional readout for a coordinated series of membrane and cytoskeletal events, and it is activated by the small GTPase, Rac. Gelsolin null fibroblasts have increased Rac expression (7Azuma T. Witke W. Stossel T.P. Hartwig J.H. Kwiatkowski D.J. EMBO J. 1998; 17: 1362-1370Crossref PubMed Scopus (235) Google Scholar), and Rac·GTP dissociates gelsolin-actin complexes (equivalent to uncapping) in cell extracts but not purified gelsolin-actin complexes (10Arcaro A. J. Biol. Chem. 1998; 273: 805-813Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar). These results suggest that gelsolin is a downstream effector of Rac, but there are additional steps between Rac and gelsolin activation/inactivation. A number of studies suggest that linkage through the type I phosphatidylinositol 5-kinases (PIP5KIs), the major enzymes that synthesize PIP2 (reviewed in Refs. 11Fruman D.A. Meyers R.E. Cantley L.C. Annu. Rev. Biochem. 1998; 67: 481-507Crossref PubMed Scopus (1319) Google Scholar and 12Anderson R.A. Boronenkov I.V. Doughman S.D. Kunz J. Loijens J.C. J. Biol. Chem. 1999; 274: 9907-9910Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar), is an attractive possibility. PIP5KIs coimmunoprecipitate with Rac (13Tolias K.F. Cantley L.C. Carpenter C.L. J. Biol. Chem. 1995; 270: 17656-17659Abstract Full Text Full Text PDF PubMed Scopus (424) Google Scholar) and also Rho (14Chong L.D. Traynor-Kaplan A. Bokoch G.M. Schwartz M.A. Cell. 1994; 79: 507-513Abstract Full Text PDF PubMed Scopus (594) Google Scholar), a small GTPase that promotes stress fiber formation. PIP5KIs may thus be incorporated into signaling complexes that are targeted to the plasma membrane through Rac·GTP or Rho·GTP. This increases the local concentration of PIP2 in membrane microdomains to selectively activate downstream cascades (reviewed in Refs. 12Anderson R.A. Boronenkov I.V. Doughman S.D. Kunz J. Loijens J.C. J. Biol. Chem. 1999; 274: 9907-9910Abstract Full Text Full Text PDF PubMed Scopus (240) Google Scholar and15Toker A. Curr. Opin. Cell Biol. 1998; 10: 254-261Crossref PubMed Scopus (245) Google Scholar). PIP2 has a pivotal role in the phosphoinositide cycle that drives signaling, cytoskeletal organization, and membrane trafficking (reviewed in Ref. 15Toker A. Curr. Opin. Cell Biol. 1998; 10: 254-261Crossref PubMed Scopus (245) Google Scholar). Numerous cytoskeletal proteins are affected by PIP2 in vitro. They include gelsolin family proteins (16Janmey P.A. Stossel T.P. Nature. 1987; 325: 362-364Crossref PubMed Scopus (496) Google Scholar), profilin (17Lassing I. Lindberg U. Nature. 1985; 314: 472-474Crossref PubMed Scopus (639) Google Scholar), capping protein (18Schafer D.A. Jennings P.B. Cooper J.A. J. Cell Biol. 1996; 135: 169-179Crossref PubMed Scopus (337) Google Scholar), ADF/cofilin (19Yonezawa N. Nishida E. Iida K. Yahara I. Sakai H. J. Biol. Chem. 1990; 265: 8382-8386Abstract Full Text PDF PubMed Google Scholar), α-actinin (20Fukami K. Furuhashi K. Inagaki M. Endo T. Hatano S. Takenawa T. Nature. 1992; 359: 150-152Crossref PubMed Scopus (304) Google Scholar), vinculin (21Gilmore A.P. Burridge K. Nature. 1996; 381: 531-535Crossref PubMed Scopus (457) Google Scholar), ezrin/radixin/moesin (22Hirao M. Sato N. Kondo T. Yonemura S. Monden M. Sasaki T. Takai Y. Tsukita S. J. Cell Biol. 1996; 135: 37-51Crossref PubMed Scopus (511) Google Scholar), and WASp family proteins (23Miki H. Miura K. Takenawa T. EMBO J. 1996; 15: 5326-5335Crossref PubMed Scopus (555) Google Scholar). The latter four proteins are activated by PIP2, whereas the first four are inactivated by PIP2. Ezrin/radixin/moesin, ADF/cofilin, and WASp are reviewed in this series (24Higgs H.N. Pollard T.D. J. Biol. Chem. 1999; 274: 32531-32534Abstract Full Text Full Text PDF PubMed Scopus (207) Google Scholar, 25Tsukita S. Yonemura S. J. Biol. Chem. 1999; 274: 34507-34510Abstract Full Text Full Text PDF PubMed Scopus (401) Google Scholar, 26Carlier M.-F. Ressad F. Pantaloni D. J. Biol. Chem. 1999; 274: 33827-33830Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar). The challenge will be to identify cytoskeletal proteins that are physiologically regulated by PIP2 and determine how they are differentially regulated. PIP2 involvement in cytoskeletal regulation is supported by experiments that manipulate PIP2 content in intact cells and in cell-free models. Microinjection of a monoclonal antibody to PIP2 prevents stress fiber and focal adhesion formation (21Gilmore A.P. Burridge K. Nature. 1996; 381: 531-535Crossref PubMed Scopus (457) Google Scholar). PIP5KI overexpression induces the formation of short actin bundles (27Shibasaki Y. Ishihara H. Kizuki N. Asano T. Oka Y. Yazaki Y. J. Biol. Chem. 1997; 272: 7578-7581Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar) and increases the movement of dynamic actin spots containing a number of actin regulatory proteins (28Schafer D.A. Welch M.D. Machesky L.M. Bridgman P.C. Meyer S.M. Cooper J.A. J. Cell Biol. 1998; 143: 1919-1930Crossref PubMed Scopus (152) Google Scholar). In contrast, overexpression of synaptojanin, the inositol polyphosphate 5-phosphatase that dephosphorylates PIP2, reduces actin stress fibers (29Sakisaka T. Itoh T. Miura K. Takenawa T. Mol. Cell. Biol. 1997; 17: 3841-3849Crossref PubMed Scopus (147) Google Scholar). Moreover, Hartwig et al. (30Hartwig J.H. Bokoch G.M. Carpenter C.L. Janmey P.A. Taylor L.A. Toker A. Stossel T.P. Cell. 1995; 82: 643-653Abstract Full Text PDF PubMed Scopus (613) Google Scholar) were able to reconstitute the entire pathway between thrombin stimulation, Rac activation, PIP2 synthesis, and barbed end nucleated actin assembly in permeabilized platelets. However, in neutrophils and other systems, the relation is less clear. Although Rac·GTP dissociates gelsolin-actin complexes (10Arcaro A. J. Biol. Chem. 1998; 273: 805-813Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar) and stimulates PIP2synthesis, it does not promote actin assembly in lysates (31Zigmond S.H. Joyce M. Borleis J. Bokoch G.M. Devreotes P.N. J. Cell Biol. 1997; 138: 363-374Crossref PubMed Scopus (145) Google Scholar). Instead, Cdc42, which stimulates filopodia formation in cells, promotes de novo actin assembly in vitro, in a that is through WASp and the R. H. M. T. Takenawa T. Cell. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The of and the of small and PIP2 nucleated actin assembly in and in of cells may be by that there are multiple for actin membrane may the between Rac and actin polymerization more that between and Gelsolin overexpression increases membrane ruffling and chemotaxis Stossel T.P. Kwiatkowski D.J. PubMed Scopus Google Scholar, Yin H.L. J. Cell Biol. 1997; 138: PubMed Scopus Google Scholar), consistent with the role of gelsolin in dynamic actin a gelsolin that but does not sever and the capping protein also cell motility K. Yin H.L. J. Cell Biol. 1995; PubMed Scopus Google Scholar, C. I. Bridgman P.C. Cooper J.A. Cell. 1995; 81: Full Text PDF PubMed Scopus Google Scholar). A pure capping proteins are to be less in actin because they do not the number of actin filaments and uncapping) and in the Prologue to this series (74Yin H.L. Stull J.T. J. Biol. Chem. 1999; 274: 32529-32530Abstract Full Text Full Text PDF PubMed Scopus (32) Google These results that may be to actin dynamics. will be required to between the of severing and studies that gelsolin may have other in to cytoskeletal gelsolin Yin H.L. J. Cell Biol. 1997; 138: PubMed Scopus Google Scholar) and K. Yin H.L. J. Cell Biol. 1995; PubMed Scopus Google Scholar) and in a in and in vitro. These PIP2 Yin H.L. J. Cell Biol. 1997; 138: PubMed Scopus Google Scholar), suggesting that gelsolin or with other proteins for their This potent effect may be by the of PIP2 molecules within the membrane L.A. J. Kosik K.S. Janmey P.A. Biophys. J. 1997; Full Text PDF PubMed Scopus Google Scholar). In these results suggest that as PIP2 content and during signaling, between proteins a for as as regulation of phosphoinositide This is as more proteins are Gelsolin with and it the of phosphatidylinositol and as (reviewed in Refs. 1Liu Y.T. Rozelle A.L. Yin H.L. Maruta H. Kohama K. G Proteins, Cytoskeleton and Cancer. R. G. Landes Company, Austin, TX1998: 19-35Google Scholar and D.J. Curr. Opin. Cell Biol. 1999; 11: 103-108Crossref PubMed Scopus (326) Google Scholar). Gelsolin is by in vitro, and is by PIP2 V. J. J. 1997; PubMed Scopus Google Scholar). The of these and has not been Gelsolin is a for S. Azuma T. C. A. J. K. K. Kwiatkowski D.J. 1997; PubMed Scopus Google Scholar, S. H. H. M. N. Y. U. S. A. 1998; PubMed Scopus Google Scholar), the effector in the and apoptotic Gelsolin by Ca2+ to sever actin filaments (see also “Structural Basis for Ca2+ and it the membrane cytoskeleton to cause a of of the severing induces whereas gelsolin null neutrophils have a of S. Azuma T. C. A. J. K. K. Kwiatkowski D.J. 1997; PubMed Scopus Google Scholar). These findings the importance of gelsolin severing to the of the cell and to selectively activate gelsolin The role of gelsolin is supported by the that most cells have reduced have gelsolin expression Y. H.L. D. M. R. J. 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The binds a actin only Ca2+ is M. and H. for The binds actin molecules to sever and in the of severing by gelsolin the as a regulatory to severing by the In the severing by the through to the filament (3Selden L.A. Kinosian H.J. Newman J. Lincoln B. Hurwitz C. Gershman L.C. Estes J.E. Biophys. J. 1998; 75: 3101-3109Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar). are of and a is will results from the first and review results from the “Structural Basis for Ca2+ The J.T. Nature. PubMed Scopus Google Scholar) how a gelsolin binds of the between Stossel T.P. S.H. J.E. Yin H.L. Nature. PubMed Scopus Google L.D. J. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar), it can be as a for how the other The gelsolin in the of Ca2+ that gelsolin has a in the of Ca2+ L.D. J. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar). are by a which and “Structural Basis for Ca2+ each the first and and and for the and are into a that is with actin This binds actin in the of It also that major changes in each and in the relation between the to actin A of a gelsolin attached to an actin filament (4McGough A. Chiu W. Way M. Biophys. J. 1998; 74: 764-772Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar) at the of the that is The that gelsolin binds to actin molecules in filament and The between the and and the and the filament that there be changes and can The and of the or may have to to the between and in Refs. L.D. J. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar and A. Curr. Opin. Biol. 1998; PubMed Scopus Google Scholar). A for how this of may is in The of how gelsolin is in the Ca2+ and how Ca2+ gelsolin are clearly because they to and apoptotic Although gelsolin first identified as a protein that binds Ca2+ with H.L. K.S. Stossel T.P. J. Biol. Chem. Full Text PDF PubMed Google Scholar), studies that gelsolin with Ca2+ is more gelsolin have at with and B. S. A. 1995; PubMed Scopus Google Scholar). and are J.T. Nature. PubMed Scopus Google J. B. M. R. 1995; PubMed Scopus Google Scholar), C. M. V. D. H. and S. for gelsolin can more Ca2+ a that gelsolin binds only Ca2+ in the of and they D. A. J. Biochem. 1999; PubMed Scopus Google Scholar). The challenge will be to determine which of the identified are physiologically and how their gelsolin severing is at which is within the during A small in also reduces the for severing H.J. Newman J. Lincoln B. L.A. Gershman L.C. Estes J.E. Biophys. J. 1998; 75: Full Text Full Text PDF PubMed Scopus Google Scholar, J.A. Janmey P.A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, Yin H.L. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus (77) Google Scholar), suggesting that gelsolin can these signals to generate in and studies that Ca2+ gelsolin by a in the to the The that the of gelsolin has a that an with a short The is in close with the actin of and may as a to actin by the in the of This is the The importance of the in Ca2+ regulation is supported by of the the Ca2+ concentration for activation of severing from to whereas of the entire the Ca2+ requirement for severing Janmey P.A. Yin H.L. J. Cell Biol. PubMed Scopus Google the in at Ca2+ but not that at Ca2+ H.J. Newman J. Lincoln B. L.A. Gershman L.C. Estes J.E. Biophys. J. 1998; 75: Full Text Full Text PDF PubMed Scopus Google Scholar, J.T. 1997; PubMed Scopus Google Therefore, the is the major that the the to the severing Gelsolin is the gelsolin family proteins (see Gelsolin in Ca2+ regulation of to the through It may have the to regulation of severing and capping and to with Ca2+ regulation during by the severing from the regulatory has a for many it is the for gelsolin. The can be because a of the with actin and Ca2+ has As discussed in the of and are into an L.D. J. Cell. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar) In the of the is and are their from and new with into the by and an coordinated by and These results that that there are during Ca2+ Although there is for gelsolin-actin in cells (reviewed in Ref. 1Liu Y.T. Rozelle A.L. Yin H.L. Maruta H. Kohama K. G Proteins, Cytoskeleton and Cancer. R. G. Landes Company, Austin, TX1998: 19-35Google Scholar), gelsolin uncapping after severing cannot be by This is because a Ca2+ is between gelsolin and and it is to J.T. Nature. PubMed Scopus Google Scholar). PIP2 (16Janmey P.A. Stossel T.P. Nature. 1987; 325: 362-364Crossref PubMed Scopus (496) Google Scholar, Yin H.L. Chem. 1999; Scholar), are the only known that gelsolin severing and gelsolin from actin in P.A. Iida K. Yin H.L. Stossel T.P. J. Biol. Chem. 1987; Full Text PDF PubMed Google Scholar). Gelsolin binds PIP2 with Yin H.L. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus (77) Google Scholar). is by Ca2+ and by Yin H.L. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus (77) Google Scholar). Gelsolin PIP2 to Yin H.L. Chem. 1999; Scholar, H. Yin H.L. 1998; PubMed Scopus Google J.H. S. T. Janmey P.A. Cantley L.C. Stossel T.P. Toker A. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar) and does not inositol (17Lassing I. Lindberg U. Nature. 1985; 314: 472-474Crossref PubMed Scopus (639) Google Scholar). Therefore, gelsolin is and by the This requirement is the with many which and the inositol with G. A. B. M.P. K.S. Cantley L.C. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar). Gelsolin can between and within and is the of the J. Janmey P.A. J. Biochem. 1999; PubMed Scopus Google Scholar). Therefore, gelsolin regulation by PIP2 does not the PIP2 but is by a relation between and with the of gelsolin to for PIP2 in response to Ca2+ and Yin H.L. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus (77) Google Scholar) and to changes in PIP2 within the membrane L.A. J. Kosik K.S. Janmey P.A. Biophys. J. 1997; Full Text PDF PubMed Scopus Google Scholar), at the number of signals that are and by gelsolin to functions. In are to the role gelsolin may have in phosphoinositide signaling (see of Gelsolin Cell and PIP2 the gelsolin and the PIP2 are to a in the between and the of in the These have an that does not the P.A. J. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar, Janmey P.A. Yin H.L. J. Biol. Chem. 1992; Full Text PDF PubMed Google Scholar). PIP2 induces a Yin H.L. J. Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus (77) Google W. R. Janmey P.A. Biophys. J. 1995; Full Text PDF PubMed Scopus Google Scholar) that may with the local required to and to actin molecules gelsolin with be required to determine this is how gelsolin and PIP2 binds to other gelsolin as of the gelsolin family that have or gelsolin have been identified (reviewed in Refs. 1Liu Y.T. Rozelle A.L. Yin H.L. Maruta H. Kohama K. G Proteins, Cytoskeleton and Cancer. R. G. Landes Company, Austin, TX1998: 19-35Google Scholar and D.J. Curr. Opin. 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Biophys. 1999; PubMed Scopus Google Scholar). these I may the actin cytoskeleton to intracellular and membrane to signaling This review has the intracellular of gelsolin and to a of how gelsolin the actin cytoskeleton in response to Ca2+ and phosphoinositide a of how actin regulatory proteins are to how they to actin within has been that gelsolin and capping protein barbed ends during platelet activation M. K. Y. T. M. F. E. T. Biochem. Biophys. 1999; PubMed Scopus Google Scholar). that filaments by gelsolin and at the barbed and can in the of ADF/cofilin, and new barbed ends are K. Witke W. Kwiatkowski D.J. Hartwig J.H. J. Cell Biol. 1996; PubMed Scopus Google Scholar). Therefore, gelsolin severing and capping can novo by by the number of filament ends and the actin F. D. C. Pantaloni D. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). These findings the of the involvement of gelsolin in actin dynamics.