Microtubules are essential for vesicular transport (endocytosis and exocytosis) as well as cell motility. Certain drugs, such as colchicine, bind to tubulin molecules and prevent their polymerization; this drug is useful in the treatment of acute attacks of gout, to prevent neutrophil migration, and to lower their ability to respond to urate crystal deposits in the tissues. Vinblastine and vincristine (Oncovin) represent another family of drugs that bind to microtubules and inhibit the formation of the mitotic spindle essential for cell division. FIGURE F.2.2.1 • Photomicrograph of Mallory bodies. Ac-These drugs are used as antimitotic and antiproliferative cumulation of keratin intermediate flaments forming intercelluagents in cancer therapy. Another drug, paclitaxel (Taxol), lar inclusions is frequently associated with specifc cell injuries. is used in chemotherapy for breast cancer. It stabilizes mi-In alcoholic liver cirrhosis, hepatocytes exhibit such inclusions crotubules, preventing them from depolymerizing (an action (arrows), which are known as Mallory bodies. Lymphocytes and opposite to that of colchicine), and thus arrests cancer cells macrophages responsible for an intense infammatory reaction in various stages of cell division. surround cells containing Mallory bodies. 900.
Actin flaments are essential for various stages of leukocyte in neuroflaments within brain tissue are characteristic of migration as well as for the phagocytotic functions of vari
Alzheimer’s disease, which produces neurofbrillary ous cells. Some chemical substances isolated from fungi, tangles containing neuroflaments and other microtubule such as cytochalasin B and cytochalasin D, prevent associated proteins.
actin polymerization by binding to the plus end of the actin Another disorder of the central nervous system,flament inhibiting lymphocyte migration, phagocytosis, and Alexander disease is associated with mutations in the cell division (cytokinesis). Several toxins of poisonous coding region of the GFAP gene. The pathologic feature of mushrooms, such as phalloidin, also bind to actin flathis disease is the presence of cytoplasmic inclusionsments, stabilizing them and preventing their depolymeriza tion. Conjugated with fuorescein dyes, derivatives of the tion of intermediate flament protein GFAP. Altered GFAP phallotoxin family (i.e., NDB-phallacidin) are frequently prevents the assembly not only of intermediate flamentsused in the laboratory to stain actin flaments (see Figs.
but also of other proteins that contribute to the structural2.45 and 2.50). Prolonged exposure of the cell to these integrity and function of astrocytes. Infants with Alexander substances can disrupt the dynamic equilibrium between disease develop leukoencephalopathy (infection of theF-actin and G-actin, causing cell death.
brain) with macrocephaly (abnormally large head), seizures, and psychomotor retardation, leading to death As noted, the molecular structure of intermediate flaments usually within the frst decade of life. is tissue specifc and consists of many different types of A prominent feature of alcoholic liver cirrhosis is the proteins. Several diseases are caused by defects in the presence of eosinophilic intracytoplasmic inclusions com-proper assembly of intermediate flaments. These defects posed predominantly of keratin intermediate flaments. have also been induced experimentally by mutations in in-These inclusions, called Mallory bodies, are visible in light termediate flament genes in laboratory animals. Changes microscopy within the hepatocyte cytoplasm (Fig. F.2.2.1).