ⓘ Cytoskeletal drugs

                                     

ⓘ Cytoskeletal drugs

Cytoskeletal drugs are small molecules that interact with actin or tubulin. These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol which stabilizes microtubules or Phalloidin which stabilizes actin filaments. Others such as Cytochalasin D bind to actin monomers and prevent them from polymerizing into filaments. Drugs such as demecolcine act by enhancing the depolymerisation of already formed filaments. Some of these drugs have multiple effects on the cytoskeleton, for example Latrunculin both prevents actin polymerization as well as enhancing its rate of depolymerization. Typically the microtubule targeting drugs can be found in the clinic where they are used therapeutically in the treatment of some forms of cancer. As a result of the lack of specificity for specific type of actin the use of these drugs in animals results in unacceptable off target effects. Despite this the actin targeting compounds are still useful tools that can be used on a cellular level to help further our understanding of how this complex part of the cells internal machinery operates. For example, Phalloidin which has been conjugated with a fluorescent probe can be used for visualizing the filamentous actin in fixed samples.

Cytochalasin D and Latrunculin both are considered toxins, which have been developed by certain fungi and sponges that both promote depolymerization of filaments. In particular, Cytochalasin D is a fungal alkaloid, while Latrunculin-a toxin that is produced by the sponges. Although they are both as a result of depolymerization, they have different mechanisms. Cytochalasin D binds to the end of F-actin and inhibits the addition of subunits. In contrast, Latrunculin binds to and sequesters G-actin, thereby adding to thread the end of F-actin. After living cells, Cytochalasin D and Latrunculin disassembly of actin cytoskeleton and inhibit the movement of cells such as locomotion.

Other toxins from sponges, such as jasplakinolide and phalloidin phallotoxins, isolated from pale toadstool in" toadstool” mushrooms, opposes the function of Cytochalasin D and Latrunculin. Jasplakinolide binds and stabilizes actin dimers due to the increase of the birth one of the first phases of g-actin polymerization, and therefore, decrease the critical concentration or the minimum concentration required for the formation of filaments. Phalloidin prevents the strands from to polymerize by binding between subunits in F-actin and locking them together. The presence of phalloidin in the cell, paralyze it, killing the cell.

Phallotoxins were isolated from A. phalloides type mushrooms, and was involved in the fatal cases of mushroom poisoning. The liver and kidneys most commonly affected when ingested toxin, and can cause symptoms such as jaundice and seizures to name a few, ultimately leading to death. Three classes of toxins can be isolated from A. phalloides: amatoxins, phallotoxins, and virotoxins. These toxins can lead to death within 2-8 hours. Similarly, phallotoxins, virotoxins to interact with actin and prevent depolymerization of the filaments. Ultimately, these toxins disrupt the functions of the cytoskeleton, paralyzing susceptible cells.

                                     
  • for controlled assembly of cytoskeletal filaments in particular locations. A number of small - molecule cytoskeletal drugs have been discovered that interact
  • Zo - 1 Zyxin Cytoskeletal drugs dos Remedios CG, Chhabra D, Kekic M, et al. April 2003 Actin binding proteins: regulation of cytoskeletal microfilaments
  • Cytochalasin D Cytochalasin E Cytochalasin F Cytochalasin H Cytochalasin J Cytoskeletal drugs Haidle, A. M. Myers, A. G. 2004 An Enantioselective, Modular
  • in pleomorphic Haloarchaea. In Haloferax volcanii, CetZ forms dynamic cytoskeletal structures required for differentiation from a plate - shaped cell form
  • on rat brain brain - derived neurotrophic factor and activity - regulated cytoskeletal - associated protein mRNA expression Neuroscience. 147 3 778 85. doi: 10
  • other important classes of IEG products include secreted proteins, cytoskeletal proteins, and receptor subunits. Some IEGs such as zif268 and Arc have
  • process is propelled by motor proteins such as dynein. Microtubules are cytoskeletal fibers that have an important role in the mitotic spindle during mitosis
  • facilitating cytoskeletal remodeling and mucosal wound repair. Structural determinants that regulate the interactions between Jak3 and cytoskeletal proteins
  • platelets decreases phosphatidylinositol 4, 5 - bisphosphate and increases cytoskeletal actin Platelets. 10 4 228 37. doi: 10.1080 09537109976077. PMID 16801097
  • In addition, cytoskeletal elements are able to interact extensively and intimately with a cell s plasma membrane. Other cytoskeletal components like