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Chapter 17 : Enteric Microbial Toxins and the Intestinal Epithelial Cytoskeleton

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Enteric Microbial Toxins and the Intestinal Epithelial Cytoskeleton, Page 1 of 2

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Abstract:

The cytoskeleton provides structure and organization to the epithelial cell. In addition to providing support and rigidity on demand, the cytoskeleton mediates adhesion of cells to surfaces and to each other, anchoring of proteins into the plasma membrane, and, to a large extent, control of cellular processes. The cytoskeleton of epithelial cells, as in most mammalian cells, is composed of three major structures: microtubules, intermediate filaments, and microfilaments. Epithelial cells adhere to one another at their lateral surfaces through desmosomes, adherens junctions, and tight junctions (TJs) and to a surrounding basal lamina through hemidesmosomes and focal contacts. Given the many important roles of the epithelial cytoskeleton, it should come as no surprise that bacterial toxins have evolved to subvert these functions. toxin (BFT) was the first bacterial toxin identified to remodel the intestinal epithelial cytoskeleton and F-actin architecture via cleavage of a cell surface molecule. Enteric toxins now provide a remarkable set of tools with which to dissect the complex interactions of the epithelial cytoskeleton. The field lies at the nexus of bacteriology, protein chemistry, and cell biology and provides a prominent example of synergistic research among scientific disciplines.

Citation: Nataro J, Sears C, Fasano A, Bloch R. 2003. Enteric Microbial Toxins and the Intestinal Epithelial Cytoskeleton, p 301-332. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch17

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FIGURE 1

The enterocyte cytoskeleton. The enterocyte is supported by three major structural polymers. (i) Actin microfilaments are prominent in the microvilli, the terminal web, and the membrane cytoskeleton. Actin filaments connect to several proteins and protein complexes on the inner face of the cytoplasmic membrane, including adherens junctions, focal adhesions, and transporters in the basolateral membrane. (ii) Intermediate filaments connect to desmosomes on the basolateral membrane, giving rigidity and resistance to shear forces. (iii) Microtubules provide support and serve as tracks for molecular motors. Proteins illustrated at the adherens junction are the -and -catenins and the transmembrane protein E-cadherin (“E”). TJs comprise integral membrane proteins (“1” in Fig.), including occludins and claudins, and signaling proteins (“2” in Fig.).

Citation: Nataro J, Sears C, Fasano A, Bloch R. 2003. Enteric Microbial Toxins and the Intestinal Epithelial Cytoskeleton, p 301-332. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch17
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Image of FIGURE 2
FIGURE 2

The epithelial junctional complex. TJs (zonula occludens or ZO) comprise transmembrane proteins (occludin, claudins, and JAM), which form a tight barrier in the paracellular space. Occludin and the claudins interact with the cytoskeleton via ZO-1, ZO-2, and ZO-3, and a series of downstream adapter and signaling proteins, ultimately interfacing with actin and actin-binding proteins. Basal to the ZO is the zonula adherens (ZA). This complex is attached to the apical actin belt via catenins and also to the junctional actin strands of the ZO. Catenins are involved in cellular signaling reactions–(see text).

Citation: Nataro J, Sears C, Fasano A, Bloch R. 2003. Enteric Microbial Toxins and the Intestinal Epithelial Cytoskeleton, p 301-332. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch17
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Image of FIGURE 3
FIGURE 3

The activation cycle of Rho family GTPases. Rho family GTPases are active when bound to GTP and inactive when bound to GDP. They possess intrinsic GTPase activity, which is accelerated by GAP proteins or inhibited by GEF proteins. GDI proteins stabilize the GDP-bound state. Activated GTPases are commonly bound to the plasma membrane, but become detached on inactivation. The effect shown here for Rho is activation of an effector, illustrated with an asterisk. Many effectors exist, including kinases, phosphatases, phospholipases, and adaptor proteins. See text for details.

Citation: Nataro J, Sears C, Fasano A, Bloch R. 2003. Enteric Microbial Toxins and the Intestinal Epithelial Cytoskeleton, p 301-332. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch17
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Tables

Generic image for table
TABLE 1

Major structural proteins of the cytoskeleton

Citation: Nataro J, Sears C, Fasano A, Bloch R. 2003. Enteric Microbial Toxins and the Intestinal Epithelial Cytoskeleton, p 301-332. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch17

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