http:/www.hotessay.cn 留学生论文专业定制代写网站留学生Essay写作微管的结构和功能描述微管的结构和功能-为什么干扰微管组装的药物可以用作癌症治疗?IntroductionMicrotubules form as a highly organised network of polarised tube filaments from a protein called tubulin. Its regulation is needed for processes such as mitosis, cell migration, cell signalling and cell trafficking. The microtubules themselves are regulated by several kinases and phosphatases via signalling cascades, and concomitantly by interactions with actin cytoskeleton and adhesion sites.Microtubule-targeted drugs (MTDs) constitute a major anticancer therapeutic class having properties of anti-mitotic and anti-angiogenic properties, thereby inhibiting malignant cell growth mainly by altering microtubule dynamics in both cancer and endothelial cells. The key to design of MTDs and the understanding of tumour progression regulators is the identification of proteins regulating the microtubule network.Cell Morphology and FunctionAs the name implies, microtubules are hollow tubes having an external diameter of roughly 25nm and a cell wall thickness of 5-7nm. One of their functions is to transport organelles (e.g. secretetory vesicles) through the cytoplasm, a particularly important role in nerve cells where axoplasmic flow is required. They also have a critical role in cilia and flagella movement. Microtubules originate from a complex structure known as centrosome.Between cell divisions (figure 1), the centrosome is located at the centre of a cell near the nucleus. Embedded in the centrosome are two cylindrical centrioles, arranged at right angles to each other. At the onset of cell division, a centrosome divides and the two daughter centrosomes move to opposite poles of the nucleus to form a mitotic spindleThe functions of microtubules are important to the survival of eukaryotic cells because, along with actin and intermediate filaments, microtubules constitute the cytoskeleton which offers shape and strength to the cytoplasm. It is therefore vital that we understand their fundamentals, such as what they are composed of and how their structure is both maintained and destroyed within cells.As mentioned in the introduction, the building blocks microtubules are tubulin. However, only two forms of tubulin, -tubulin and -tubulin, play a role in the formation of the microtubule structure. When the and -tubulin bind, a useful subunit called a heterodimer forms.When intracellular conditions favour assembly, tubulin heterodimers assemble into linear protofilaments, which in turn assemble into microtubules. All such assembly is subject to regulation by the cell. 11The interactions holding and -tubulin in a heterodimeric complex are strong enough that tubulin subunit rarely dissociates under normal conditions. Each tubulin subunit binds two molecules of GTP. One GTP-binding site, located in -tubulin, binds GTP irreversibly and does not hydrolyze it, whereas the second site, located on -tubulin, binds GTP reversibly and hydrolyzes it to GDP. The second site is called the exchangeable site because GDP can be displaced by GTP. The recently solved atomic structure of the tubulin subunit reveals that the non-exchangeable GTP is trapped at the interface between the and -tubulin monomers, while the exchangeable GTP lies at the surface of the subunitMicrotubules may appear to be stable but they usually oscillate between growth and shortening phases. During growth, heterodimers are added on to the end of a microtubule, and during shrinkage they come off as intact subunits. 11This active process of assembly and disassembly can be inhibited by a range of drugs that bind to many sites in the -tubulin subunit. These drugs prevent mitotic division and ultimately lead to cell death, by means of necrosis and apoptosis.The subunits are aligned end to end into a protofilament. The side-by-side packing of protofilaments forms the wall of the microtubule. In this model, the protofilaments are slightly staggered so that a-tubulin in one protofilament is in contact with a-tubulin in the neighboring protofilaments.Microtubules and Cancer TherapyThe aim of treatment in patients with cancer is cure or, if this is not possible, effective palliation of many cancers present as localised tumour masses, but surgery or radiotherapy often fails to eradicate the disease, which eventually becomes widespread. For this reason, there is a trend to incorporate systemic treatment with local treatment at the time of diagnosis. 3 The basic mechanism of anticancer drugs is the inhibition of cell proliferation processes.However if they fail to selectively target tumour cells over proliferating normal cells, this renders the drug toxic. This particularly arises in the bone marrow, gastrointestinal epithelium and hair follicles. A cytotoxic drug is said to be selective in cancer therapy if it inhibits malignant composite cells undergoing division and concomitantly allows for normal cell proliferation.An