The Role of Cyclase-associated Protein in Regulating Actin Filament Dynamics - More Than a Monomer-sequestration Factor

Overview

Journal J Cell Sci

Specialty Cell Biology

Date 2013 Aug 3

PMID 23908377

Citations 67

Authors

Shoichiro Ono

Affiliations

Soon will be listed here.

Abstract

Dynamic reorganization of the actin cytoskeleton is fundamental to a number of cell biological events. A variety of actin-regulatory proteins modulate polymerization and depolymerization of actin and contribute to actin cytoskeletal reorganization. Cyclase-associated protein (CAP) is a conserved actin-monomer-binding protein that has been studied for over 20 years. Early studies have shown that CAP sequesters actin monomers; recent studies, however, have revealed more active roles of CAP in actin filament dynamics. CAP enhances the recharging of actin monomers with ATP antagonistically to ADF/cofilin, and also promotes the severing of actin filaments in cooperation with ADF/cofilin. Self-oligomerization and binding to other proteins regulate activities and localization of CAP. CAP has crucial roles in cell signaling, development, vesicle trafficking, cell migration and muscle sarcomere assembly. This Commentary discusses the recent advances in our understanding of the functions of CAP and its implications as an important regulator of actin cytoskeletal dynamics, which are involved in various cellular activities.

Citing Articles

Nano-Scale Video Imaging of Motility Machinery by High-Speed Atomic Force Microscopy.

McArthur S, Umeda K, Kodera N Biomolecules. 2025; 15(2).

PMID: 40001560 PMC: 11852755. DOI: 10.3390/biom15020257.

Fluo-Cast-Bright: a deep learning pipeline for the non-invasive prediction of chromatin structure and developmental potential in live oocytes.

Zhang X, Baumann C, De La Fuente R Commun Biol. 2025; 8(1):141.

PMID: 39880880 PMC: 11779945. DOI: 10.1038/s42003-025-07568-0.

The actin filament pointed-end depolymerase Srv2/CAP depolymerizes barbed ends, displaces capping protein, and promotes formin processivity.

Towsif E, Shekhar S Proc Natl Acad Sci U S A. 2025; 122(5):e2411318122.

PMID: 39874286 PMC: 11804681. DOI: 10.1073/pnas.2411318122.

Candidate proteins interacting with cytoskeleton in cells from the basal airway epithelium .

Olatona O, Choudhury S, Kresman R, Heckman C Front Mol Biosci. 2024; 11:1423503.

PMID: 39139811 PMC: 11319710. DOI: 10.3389/fmolb.2024.1423503.

Multicomponent depolymerization of actin filament pointed ends by cofilin and cyclase-associated protein depends upon filament age.

Towsif E, Miller B, Ulrichs H, Shekhar S bioRxiv. 2024; .

PMID: 38659736 PMC: 11042253. DOI: 10.1101/2024.04.15.589566.

References

Perelroizen I, Didry D, Christensen H, Chua N, Carlier M . Role of nucleotide exchange and hydrolysis in the function of profilin in action assembly. J Biol Chem. 1996; 271(21):12302-9. DOI: 10.1074/jbc.271.21.12302. View

Thompson J, Higgins D, Gibson T . CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994; 22(22):4673-80. PMC: 308517. DOI: 10.1093/nar/22.22.4673. View

KINOSIAN H, Selden L, ESTES J, Gershman L . Nucleotide binding to actin. Cation dependence of nucleotide dissociation and exchange rates. J Biol Chem. 1993; 268(12):8683-91. View

Polet D, Lambrechts A, Ono K, Mah A, Peelman F, Vandekerckhove J . Caenorhabditis elegans expresses three functional profilins in a tissue-specific manner. Cell Motil Cytoskeleton. 2005; 63(1):14-28. PMC: 2575421. DOI: 10.1002/cm.20102. View

Mockrin S, Korn E . Acanthamoeba profilin interacts with G-actin to increase the rate of exchange of actin-bound adenosine 5'-triphosphate. Biochemistry. 1980; 19(23):5359-62. DOI: 10.1021/bi00564a033. View

Yusof A, Jaenicke E, Pedersen J, Noegel A, Schleicher M, Hofmann A . Mechanism of oligomerisation of cyclase-associated protein from Dictyostelium discoideum in solution. J Mol Biol. 2006; 362(5):1072-81. DOI: 10.1016/j.jmb.2006.08.008. View

Zhou X, Zhang H, Li G, Shaw B, Xu J . The Cyclase-associated protein Cap1 is important for proper regulation of infection-related morphogenesis in Magnaporthe oryzae. PLoS Pathog. 2012; 8(9):e1002911. PMC: 3435248. DOI: 10.1371/journal.ppat.1002911. View

Lin C, Lin P, Li Y, Hsu J . Capulet and Slingshot share overlapping functions during Drosophila eye morphogenesis. J Biomed Sci. 2012; 19:46. PMC: 3411472. DOI: 10.1186/1423-0127-19-46. View

Nozumi M, Togano T, Takahashi-Niki K, Lu J, Honda A, Taoka M . Identification of functional marker proteins in the mammalian growth cone. Proc Natl Acad Sci U S A. 2009; 106(40):17211-6. PMC: 2761339. DOI: 10.1073/pnas.0904092106. View

10.

Dodatko T, Fedorov A, Grynberg M, Patskovsky Y, Rozwarski D, Jaroszewski L . Crystal structure of the actin binding domain of the cyclase-associated protein. Biochemistry. 2004; 43(33):10628-41. DOI: 10.1021/bi049071r. View

11.

Agrawal P, Joshi M, Savic T, Chen Z, Beggs A . Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance. Hum Mol Genet. 2012; 21(10):2341-56. PMC: 3335316. DOI: 10.1093/hmg/dds053. View

12.

Peche V, Holak T, Burgute B, Kosmas K, Kale S, Wunderlich F . Ablation of cyclase-associated protein 2 (CAP2) leads to cardiomyopathy. Cell Mol Life Sci. 2012; 70(3):527-43. PMC: 11113306. DOI: 10.1007/s00018-012-1142-y. View

13.

Yamazaki K, Takamura M, Masugi Y, Mori T, Du W, Hibi T . Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. Lab Invest. 2009; 89(4):425-32. DOI: 10.1038/labinvest.2009.5. View

14.

Hubberstey A, Yu G, Loewith R, Lakusta C, Young D . Mammalian CAP interacts with CAP, CAP2, and actin. J Cell Biochem. 1996; 61(3):459-66. DOI: 10.1002/(SICI)1097-4644(19960601)61:3%3C459::AID-JCB13%3E3.0.CO;2-E. View

15.

Zelicof A, Protopopov V, David D, Lin X, Lustgarten V, Gerst J . Two separate functions are encoded by the carboxyl-terminal domains of the yeast cyclase-associated protein and its mammalian homologs. Dimerization and actin binding. J Biol Chem. 1996; 271(30):18243-52. DOI: 10.1074/jbc.271.30.18243. View

16.

Sultana H, Rivero F, Blau-Wasser R, Schwager S, Balbo A, Bozzaro S . Cyclase-associated protein is essential for the functioning of the endo-lysosomal system and provides a link to the actin cytoskeleton. Traffic. 2005; 6(10):930-46. DOI: 10.1111/j.1600-0854.2005.00330.x. View

17.

Barrero R, Umeda M, Yamamura S, Uchimiya H . Arabidopsis CAP regulates the actin cytoskeleton necessary for plant cell elongation and division. Plant Cell. 2002; 14(1):149-63. PMC: 150557. DOI: 10.1105/tpc.010301. View

18.

Yusof A, Hu N, Wlodawer A, Hofmann A . Structural evidence for variable oligomerization of the N-terminal domain of cyclase-associated protein (CAP). Proteins. 2004; 58(2):255-62. DOI: 10.1002/prot.20314. View

19.

Pollard T, Goldberg I, Schwarz W . Nucleotide exchange, structure, and mechanical properties of filaments assembled from ATP-actin and ADP-actin. J Biol Chem. 1992; 267(28):20339-45. View

20.

Goldschmidt-Clermont P, Furman M, Wachsstock D, Safer D, Nachmias V, Pollard T . The control of actin nucleotide exchange by thymosin beta 4 and profilin. A potential regulatory mechanism for actin polymerization in cells. Mol Biol Cell. 1992; 3(9):1015-24. PMC: 275662. DOI: 10.1091/mbc.3.9.1015. View