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Gelsolin (amyloidosis, Finnish type)
PDB rendering based on 1c0f.
Available structures: 1c0f, 1c0g, 1d0n, 1d4x, 1dej, 1eqy, 1esv, 1h1v, 1kcq, 1mdu, 1nlv, 1nm1, 1nmd, 1nph, 1p8x, 1p8z, 1rgi, 1t44, 1yag, 1yvn, 2ff3, 2ff6, 2fgh, 2fh1, 2fh2, 2fh3, 2fh4
Symbol(s) GSN; DKFZp313L0718
External IDs OMIM: 137350 MGI: 95851 Homologene: 147
RNA expression pattern

More reference expression data

Human Mouse
Entrez 2934 227753
Ensembl ENSG00000148180 ENSMUSG00000026879
Uniprot P06396 Q3TGJ9
Refseq NM_000177 (mRNA)
NP_000168 (protein)
NM_146120 (mRNA)
NP_666232 (protein)
Location Chr 9: 123.07 - 123.13 Mb Chr 2: 35.1 - 35.13 Mb
Pubmed search [1] [2]

Gelsolin is an actin-binding protein that is a key regulator of actin filament assembly and disassembly. Gelsolin is one of the most potent members of the actin-severing gelsolin/villin superfamily, as it severs with nearly 100% efficiency.[1] Gelsolin is located intracellularly (in cytosol and mitochondria) and extracellularly (in blood plasma).[2]



Gelsolin is an 82-kD protein with six homologous subdomains, referred to as S1-S6. Each subdomain is composed of a five-stranded β-sheet, flanked by two α-helices, one positioned perpendicular with respect to the strands and one positioned parallel. The N-terminal (S1-S3) forms an extended β-sheet, as does the C-terminal (S4-S6).[3]


Among the lipid binding actin regulatory proteins, gelsolin (along with cofilin) is one of the few that exhibit preferential binding towards polyphosphoinositide (PPIs).[4] The binding sequences in gelsolin closely resemble the motifs in the other PPI-binding proteins.[4]

Gelsolin's activity is stimulated by calcium ions (Ca2+).[1] Although the protein retains its overall structural integrity in both activated and deactivated states, the S6 helical tail moves like a latch depending on the concentration of calcium ions.[5] The C-terminal end detects the calcium concentration within the cell. When there is no Ca2+ present, the tail of S6 shields the actin-binding sites on one of S2's helices.[3] When a calcium ion attaches to the S6 tail, however, it straightens, exposing the S2 actin-binding sites.[5] The N-terminal is directly involved in the severing of actin. S2 and S3 bind to the actin before the binding of S1 severs actin-actin bonds and caps the barbed end.[4]

Gelsolin can be inhibited by a local rise in the concentration of phosphatidylinositol (4,5)-bisphosphate (PIP2), a PPI. This is a two step process. Firstly, (PIP2) binds to S2 and S3, inhibiting gelsolin from actin side binding. Then, (PIP2) binds to gelsolin’s S1, preventing gelsolin from severing actin, although (PIP2) does not bind directly to gelsolin's actin-binding site.[4]

Gelsolin's severing of actin, in contrast to the severing of microtubules by katanin, does not require any extra energy input.

Cellular Function

As an important actin regulator, gelsolin plays a role in podosome formation (along with Arp3, cortactin, and Rho GTPases).[6]

Gelsolin also inhibits apoptosis by stabilizing the mitochondria [2]. Prior to cell death, mitochondria normally lose membrane potential and become more permeable. Gelsolin can impede the release of cytochrome C, obstructing the signal amplification that would have led to apoptosis.

Actin can be cross-linked into a gel by actin cross-linking proteins. Gelsolin can turn this gel into a sol, hence the name gelsolin.

Organismal Relevance

Research in mice suggests that gelsolin, like other actin-severing proteins, is not expressed to a significant degree until after the early embryonic stage--approximately 2 weeks in murine embryos.[7] In adult specimens, however, gelsolin is particularly important in motile cells, such as blood platelets. Mice with null gelsolin-coding genes undergo normal embryonic development, but the deformation of their blood platelets reduced their motility, resulting in a slower response to wound healing.[7]

An insufficiency of gelsolin in mice has also been shown to cause increased permeability of the vascular pulmonary barrier, suggesting that gelsolin is important in the response to lung injury.[8]


  1. ^ a b Sun, H., Yamamoto, M., Mejillano, M., Yin, H. (1999). "Gelsolin, a Multifunction Actin Regulatory Protein". J Biol Chem 274 (47): 33179–33182.
  2. ^ a b Koya, R., Fujita, H., Shimizu, S., Ohtsu, M., Takimoto, M., Tsujimoto, Y., Kuzumaki, N. (2000). "Gelsolin Inhibits Apoptosis by Blocking Mitochondrial Membrane Potential Loss and Cytochrome C Release". J Biol Chem 275 (20): 15343-15349. PMID 10809769.
  3. ^ a b Kiselar, J., Janmey, P., Almo, S., Chance, M. (2003). "Visualizing the Ca2+-dependent activation of gelsolin by using synchrotron footprinting". PNAS 100 (7): 3942-3947. PMID 12655044.
  4. ^ a b c d Yu, F., Sun, H., Janmey, P., Yin, H. (1992). "Identification of a Polyphosphoinositide-binding Sequence in an Actin Monomer-binding Domain of Gelsolin". J Biol Chem 267 (21): 14616-14621. PMID 1321812.
  5. ^ a b Burtnick, L, Urosev, D., Irobi, E., Narayan, K., Robinson, R. (2004). "Structure of the N-terminal half of gelsolin bound to actin: roles in severing, apoptosis and FAF". The EMBO Journal 23: 2713–2722. PMID 15215896.
  6. ^ Varon, C., Tatin, F., Moreau, V., Obberghen-Schilling, E., Fernandez-Sauze, S., Reuzeau, E., Kramer, I., Génot, E. (2005). "Transforming Growth Factor β Induces Rosettes of Podosomes in Primary Aortic Endothelial Cells". Molecular and Cellular Biology 26 (9): 3582-3594. PMID 16611998.
  7. ^ a b Witke, W., Sharpe, A., Hartwig, J., Azuma, T., Stossel, T., Kwiatkowski, D. (1995). "Hemostatic, Inflammatory, and Fibroblast Responses Are Blunted in Mice Lacking Gelsolin". Cell 81: 41-51. PMID 7720072.
  8. ^ Becker, P., Kazi, A., Wadgaonkar, R., Pearse, D., Kwiatkowski, D., Garcia, J. (2003). "Pulmonary Vascular Permeability and Ischemic Injury in Gelsolin-Deficient Mice". American Journal of Respiratory Cell and Molecular Biology 28: 478-484. PMID 12654637.

See also

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Gelsolin". A list of authors is available in Wikipedia.
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