CapZ, also known as CAPZ, CAZ1 and CAPPA1, is a capping protein that caps the barbed end of actin filaments in muscle cells.[1]

Structure

CapZ is a heterodimeric molecule, made up of an α and β subunit.[2] The α and β subunits are similar in structure. Each subunit is divided into three domains and a shared C-terminal extension.[3] Helix 1-3 is an N-terminal that is composed of three antiparallel helices that are arranged in an up, down, up pattern. Helix 4 is a C-terminal made up of an antiparallel β sheet which is composed of five β strands. On one side of the C-terminal, there is a shorter N-terminal helix and a long C-terminal helix. This long C-terminal helix makes up helix 5. The final helix, helix 6 differs in the α and β subunits. The β subunit is longer than the α subunit.

Function

This image shows the structures of Cap32/34 superposed onto CapZ (in green) over the Cα positions of the entire CP molecules.[4]

Actin stabilisation

The main function of CapZ is to cap the barbed (plus) end of actin filaments in muscle cells. It is located in the Z band of the muscle sarcomere. This protein helps to stabilize the actin filaments protecting it from assembly and disassembly. The activity regulation of this protein can be done by other regulatory proteins that bind to the actin filaments blocking the CapZ, hence allowing assembly.[5]

Cell signalling

CapZ is known to play a role in cell signaling, as it regulates PKC activity in cardiac cells.[6]

Cell movement

CapZ plays a role in cell movement (cell crawling) by controlling the lengths of the microfilaments. When CapZ is inhibited by regulating factors, microfilament polymerization or depolymerization occurs allowing lamellipodia and filopodia to grow out or retract. This polymerization and depolymerization gives the cell the appearance of crawling. When CapZ binds, it halts both of these processes.[7]

Regulation

Experimentation on chicken muscles have indicated that there are certain proteins that inhibit CapZ from binding. This includes PIP2 and other phospholipids. These molecules bind to CapZ itself to prevent it from binding to actin. However, introduction of certain detergents (in this case Triton X 100) prevent the binding of these molecules to CapZ; in turn allowing it to bind to the microfilament.[8][9] Competition for actin binding sites can also regulate CapZ binding, as seen with filament elongation factors. These factors include ENA/VASP (enabled/vasodilator-stimulated phosphoprotein).[10] CapZ is not regulated by calcium or calmodulin, as seen with other capping proteins, such as Gelsolin.[11]

Clinical significance

Cardiac health

A modest reduction in cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury.[12]

Genes

References

  1. ↑ "Actin Filament Capping Protein (CapZ): The Story After Crystal Structure Elucidation" (PDF). Retrieved November 11, 2019.
  2. ↑ Yamashita, Atsuko; Maeda, Kayo; Maéda, Yuichiro (2003-04-01). "Crystal structure of CapZ: structural basis for actin filament barbed end capping". The EMBO Journal. 22 (7): 1529–1538. doi:10.1093/emboj/cdg167. ISSN 0261-4189. PMC 152911. PMID 12660160.
  3. ↑ Yamashita, Atsuko; Maeda, Kayo; Maéda, Yuichiro (1 April 2003). "Crystal structure of CapZ: structural basis for actin filament barbed end capping". The EMBO Journal. 22 (7): 1529–1538. doi:10.1093/emboj/cdg167. PMC 152911. PMID 12660160.
  4. ↑ Eckert, C.; Goretzki, A.; Faberova, M.; Kollmar, M. (2012). "Conservation and divergence between cytoplasmic and muscle-specific actin capping proteins: Insights from the crystal structure of cytoplasmic Cap32/34 from Dictyostelium discoideum". BMC Structural Biology. 12: 12. doi:10.1186/1472-6807-12-12. PMC 3472329. PMID 22657106.
  5. ↑ Lodish, Harvey; Berk, Arnold; Kaiser, Chris; Krieger, Monty; Bretscher, Antony; Ploegh, Hidde; Amon, Angelika; Scott, Matthew (2012-05-02). Molecular Cell Biology (7th ed.). W. H. Freeman. p. 783. ISBN 9781429234139.
  6. ↑ Yang, Fenghua; Aiello, David L.; Pyle, W. Glen (2008-02-01). "Cardiac myofilament regulation by protein phosphatase type 1alpha and CapZ". Biochemistry and Cell Biology. 86 (1): 70–78. doi:10.1139/o07-150. ISSN 1208-6002. PMID 18364747.
  7. ↑ Hug, Christopher; Jay, Patrick Y.; Reddy, Indira; McNally, James G.; Bridgman, Paul C.; Elson, Elliot L.; Cooper, John A. (May 1995). "Capping protein levels influence actin assembly and cell motility in dictyostelium". Cell. 81 (4): 591–600. doi:10.1016/0092-8674(95)90080-2. PMID 7758113.
  8. ↑ "CapZ". www.bms.ed.ac.uk. Retrieved 2016-11-06.
  9. ↑ Heiss, Steven; Cooper, John (June 24, 1991). "Regulation of CapZ, an actin capping protein of chicken muscle, by anionic phospholipids". Biochemistry. 30 (36): 8753–8758. doi:10.1021/bi00100a006. PMID 1653607.
  10. ↑ Edwards, Marc; Zwolak, Adam; Schafer, Dorothy A.; Sept, David; Dominguez, Roberto; Cooper, John A. (2014-10-01). "Capping protein regulators fine-tune actin assembly dynamics". Nature Reviews Molecular Cell Biology. 15 (10): 677–689. doi:10.1038/nrm3869. ISSN 1471-0072. PMC 4271544. PMID 25207437.
  11. ↑ Gremm, D.; Wegner, A. (2000-07-01). "Gelsolin as a calcium-regulated actin filament-capping protein". European Journal of Biochemistry. 267 (14): 4339–4345. doi:10.1046/j.1432-1327.2000.01463.x. ISSN 0014-2956. PMID 10880956.
  12. ↑ Yang, Feng Hua; Pyle, W. Glen (March 2012). "Reduced cardiac CapZ protein protects hearts against acute ischemia–reperfusion injury and enhances preconditioning". Journal of Molecular and Cellular Cardiology. 52 (3): 761–772. doi:10.1016/j.yjmcc.2011.11.013. PMID 22155006.
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