Cytochalasins are

fungal A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the tradit ...

metabolites In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

that have the ability to bind to

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 ...

filaments and block

polymerization In polymer chemistry, polymerization (American English), or polymerisation (British English), is a process of reacting monomer molecules together in a chemical reaction to form polymer chains or three-dimensional networks. There are many fo ...

and the elongation of actin. As a result of the inhibition of actin polymerization, cytochalasins can change cellular morphology, inhibit cellular processes such as

cell division Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...

, and even cause cells to undergo

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. Cytochalasins have the ability to permeate cell membranes, prevent cellular translocation and cause cells to enucleate. Cytochalasins can also have an effect on other aspects of biological processes unrelated to actin polymerization. For example, cytochalasin A and cytochalasin B can also inhibit the transport of monosaccharides across the cell membrane, cytochalasin H has been found to regulate plant growth, cytochalasin D inhibits protein synthesis and cytochalasin E prevents angiogenesis.

Binding to actin filaments

Cytochalasins are known to bind to the barbed, fast growing plus ends of

microfilaments Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other p ...

, which then blocks both the assembly and disassembly of individual actin monomers from the bound end. Once bound, cytochalasins essentially cap the end of the new actin filament. One cytochalasin will bind to one actin filament. Studies done with cytochalasin D (CD) have found that CD-actin dimers contain ATP-bound actin upon formation. These CD-actin dimers are reduced to CD-actin monomers as a result of ATP hydrolysis. The resulting CD-actin monomer can bind ATP-actin monomer to reform the CD-actin dimer. CD is very effective; only low concentrations (0.2 μM) are needed to prevent membrane ruffling and disrupt

treadmilling In molecular biology, treadmilling is a phenomenon observed within protein filaments of the cytoskeletons of many cells, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end ...

. The effects of many different cytochalasins on actin filaments were analyzed and higher concentrations (2-20 μM) of CD were found to be needed to remove stress fibers. In contrast, latrunculin inhibits actin filament polymerization by binding to actin monomers.

Uses and applications of cytochalasins

Actin microfilaments have been widely studied using cytochalasins. Due to their chemical nature, cytochalasins can help researchers understand the importance of actin in various biological processes. The use of cytochalasins has allowed researchers to better understand actin polymerization, cell motility, ruffling, cell division, contraction, and cell stiffness. The use of cytochalasins has been so important to understanding cytoskeletal movement and many other biological processes, researchers have created two synthetic cytochalasins. Cytochalasin has found practical application in

thromboelastometry Thromboelastometry (TEM), previously named rotational thromboelastography (ROTEG) or rotational thromboelastometry (ROTEM), is an established viscoelastic method for hemostasis testing in whole blood. It is a modification of traditional thrombo ...

(TEM) whole blood assays for the assessment of

fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

and fibrin polymerization disorders in the FIBTEM assay on ROTEM. This test is based on the principle that cytochalasin D very effectively inhibits

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

function by inhibition of the contractile elements. The platelet inhibition is more effective than when platelets are blocked by GPIIb/IIIa

antagonists An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

concentration-dependent manner independent of platelet count. Therefore, fibrinogen deficiency or fibrin polymerization disorders can be rapidly detected.

Chemical structures

File:Cytochalasin A.png, Cytochalasin A File:Cytochalasin B.png, Cytochalasin B File:Cytochalasin C.png, Cytochalasin C File:Cytochalasin D.png, Cytochalasin D File:Cytochalasin E.png, Cytochalasin E File:Cytochalasin F.png, Cytochalasin F File:Cytochalasin H.png, Cytochalasin H File:Cytochalasin J.png, Cytochalasin J

References

{{Toxins Mycotoxins Actin inhibitors

Binding to actin filaments

Uses and applications of cytochalasins

Chemical structures

See also

References