Cofilin-2 Explained

Cofilin 2 (muscle) also known as CFL2 is a protein which in humans is encoded by the CFL2 gene.^{[1] [2]}

Function

Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner.^[2] Cofilin-2 is a member of the AC group of proteins that also includes cofilin-1 (CFL1) and destrin (DSTN), all of which regulate actin-filament dynamics.^{[3] [4]} The CFL2 gene encodes a skeletal muscle-specific isoform^[5] localized to the thin filaments, where it exerts its effect on actin, in part through interactions with tropomyosins.^[6]

Clinical significance

Mutations in the CFL2 gene are associated with nemaline myopathy. Deficiency of cofilin-2 may result in reduced depolymerization of actin filaments, causing their accumulation in nemaline bodies, minicores, and, possibly concentric laminated bodies.^[7]

External links

• GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy

Further reading

• Thirion C, Stucka R, Mendel B . Characterization of human muscle type cofilin (CFL2) in normal and regenerating muscle. . Eur. J. Biochem. . 268 . 12 . 3473–82 . 2001 . 11422377 . 10.1046/j.1432-1327.2001.02247.x . etal. free .
• Rual JF, Venkatesan K, Hao T . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 . etal.
• Jia L, Young MF, Powell J . Gene expression profile of human bone marrow stromal cells: high-throughput expressed sequence tag sequencing analysis. . Genomics . 79 . 1 . 7–17 . 2002 . 11827452 . 10.1006/geno.2001.6683 . etal.
• Kudryashov DS, Galkin VE, Orlova A . Cofilin cross-bridges adjacent actin protomers and replaces part of the longitudinal F-actin interface. . J. Mol. Biol. . 358 . 3 . 785–97 . 2006 . 16530787 . 10.1016/j.jmb.2006.02.029 . etal.
• Nebl G, Meuer SC, Samstag Y . Dephosphorylation of serine 3 regulates nuclear translocation of cofilin. . J. Biol. Chem. . 271 . 42 . 26276–80 . 1996 . 8824278 . 10.1074/jbc.271.42.26276 . free .
• Zhang Y, Wolf-Yadlin A, Ross PL . Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. . Mol. Cell. Proteomics . 4 . 9 . 1240–50 . 2005 . 15951569 . 10.1074/mcp.M500089-MCP200 . etal. free .
• Kimura K, Wakamatsu A, Suzuki Y . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 . etal.
• Hillier LD, Lennon G, Becker M . Generation and analysis of 280,000 human expressed sequence tags. . Genome Res. . 6 . 9 . 807–28 . 1996 . 8889549 . 10.1101/gr.6.9.807 . etal. free .
• Endo M, Ohashi K, Sasaki Y . Control of growth cone motility and morphology by LIM kinase and Slingshot via phosphorylation and dephosphorylation of cofilin. . J. Neurosci. . 23 . 7 . 2527–37 . 2003 . 12684437 . 10.1523/JNEUROSCI.23-07-02527.2003. 6742113 . etal. free .
• Coiras M, Camafeita E, Ureña T . Modifications in the human T cell proteome induced by intracellular HIV-1 Tat protein expression. . Proteomics . 6 . S63–73 . 2006 . Suppl 1 . 16526095 . 10.1002/pmic.200500437 . 42878271 . etal.
• Yang N, Higuchi O, Ohashi K . Cofilin phosphorylation by LIM-kinase 1 and its role in Rac-mediated actin reorganization. . Nature . 393 . 6687 . 809–12 . 1998 . 9655398 . 10.1038/31735 . 1998Natur.393..809Y . 4326365 . etal.
• Olsen JV, Blagoev B, Gnad F . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. . Cell . 127 . 3 . 635–48 . 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . etal. free .
• Wu Y, Yoder A, Yu D . Cofilin activation in peripheral CD4 T cells of HIV-1 infected patients: a pilot study. . Retrovirology . 5 . 1. 95 . 2008 . 18928553 . 10.1186/1742-4690-5-95 . 2576353 . etal . free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Papalouka V, Arvanitis DA, Vafiadaki E . Muscle LIM protein interacts with cofilin 2 and regulates F-actin dynamics in cardiac and skeletal muscle. . Mol. Cell. Biol. . 29 . 22 . 6046–58 . 2009 . 19752190 . 10.1128/MCB.00654-09 . 2772566 . etal.

Notes and References

1. Web site: Entrez Gene: CFL2 cofilin 2 (muscle) .
2. Gillett GT, Fox MF, Rowe PS, Casimir CM, Povey S . Mapping of human non-muscle type cofilin (CFL1) to chromosome 11q13 and muscle-type cofilin (CFL2) to chromosome 14 . Ann. Hum. Genet. . 60 . Pt 3 . 201–11 . May 1996 . 8800436 . 10.1111/j.1469-1809.1996.tb00423.x. 19565638 .
3. Bamburg JR, McGough A, Ono S . Putting a new twist on actin: ADF/cofilins modulate actin dynamics . Trends Cell Biol. . 9 . 9 . 364–70 . September 1999 . 10461190 . 10.1016/S0962-8924(99)01619-0.
4. Maciver SK, Hussey PJ . The ADF/cofilin family: actin-remodeling proteins . Genome Biol. . 3 . 5 . reviews3007 . 2002 . 12049672 . 139363 . 10.1186/gb-2002-3-5-reviews3007 . free .
5. Vartiainen MK, Mustonen T, Mattila PK . The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics . Mol. Biol. Cell . 13 . 1 . 183–94 . January 2002 . 11809832 . 65081 . 10.1091/mbc.01-07-0331 . etal.
6. Ono S, Ono K . Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics . J. Cell Biol. . 156 . 6 . 1065–76 . March 2002 . 11901171 . 2173459 . 10.1083/jcb.200110013 .
7. Agrawal PB, Greenleaf RS, Tomczak KK, Lehtokari VL, Wallgren-Pettersson C, Wallefeld W, Laing NG, Darras BT, Maciver SK, Dormitzer PR, Beggs AH . Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2 . Am. J. Hum. Genet. . 80 . 1 . 162–7 . January 2007 . 17160903 . 1785312 . 10.1086/510402 .