CapZ, also known as CAPZ, CAZ1 and CAPPA1, is a capping protein that caps the barbed end of

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

filaments in

muscle cells A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscle ...

Structure

CapZ is a

heterodimeric In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

molecule, made up of an α and β subunit. The α and β subunits are similar in structure. Each subunit is divided into three domains and a shared C-terminal extension. 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

Orthogonal views of cytoplasmic capping protein superposed onto its homolog CapZ

Actin stabilisation

The main function of CapZ is to cap the barbed (plus) end of

filaments in

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

cells. It is located in the Z band of the muscle

sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called musc ...

. 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.

Cell signalling

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

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 The lamellipodium (plural lamellipodia) (from Latin ''lamella'', related to ', "thin sheet", and the Greek radical ''pod-'', "foot") is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional ...

and

filopodia Filopodia (singular filopodium) are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. Within the lamellipodium, actin ribs are known as ''microspikes'', and when they extend beyond the lame ...

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.

Regulation

Experimentation on chicken muscles have indicated that there are certain proteins that inhibit CapZ from binding. This includes PIP2 and other phosphoplipids. 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. 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). CapZ is not regulated by calcium or calmodulin, as seen with other capping proteins, such as Gelsolin.

Clinical significance

Cardiac health

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

Genes

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References

External links

* {{MeshName, CapZ+Actin+Capping+Protein
CyMoBase - Database of cytoskeletal and motor protein sequences
Cell adhesion proteins