H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 87
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Microvilli projecting from the apical surfaces of many epithelial cells considerably expand their surface areas.■Three major classes of cell junctions—anchoring junctions, tight junctions, and gap junctions—assemble epithelial cells into sheets and mediate communication between them (see Figures 6-1 and 6-5).■209epithelial and other tissues.
They promote strong cell–cell adhesion by mediating both lateral and intercellularinteractions.Adapter proteins that bind to the cytosolic domainof cadherins and other CAMs mediate the associationof cytoskeletal and signaling molecules with the plasmamembrane (see Figure 6-9). Strong cell–cell adhesiondepends on the linkage of the interacting CAMs to thecytoskeleton.■Tight junctions block the diffusion of proteins and somelipids in the plane of the plasma membrane, contributingto the polarity of epithelial cells. They also limit and regulate the extracellular (paracellular) flow of water andsolutes from one side of the epithelium to the other (seeFigure 6-11).■Integrins are a large family of heterodimeric cellsurface proteins that mediate both cell–cell and cell–matrix adhesions and inside-out and outside-in signalingin numerous tissues.■6.3 The Extracellular Matrixof Epithelial SheetsIn animals, the extracellular matrix helps organize cellsinto tissues and coordinates their cellular functions by activating intracellular signaling pathways that control cellgrowth, proliferation, and gene expression.
Many functions of the matrix require transmembrane adhesion receptors that bind directly to ECM components and thatalso interact, through adapter proteins, with the cytoskeleton. The principal class of adhesion receptors thatmediate cell–matrix adhesion are integrins, which were introduced in Section 6.2. However, other types of moleculesalso function as important adhesion receptors in somenonepithelial tissues.Three types of molecules are abundant in the extracellular matrix of all tissues.Highly viscous proteoglycans, a group of glycoproteinsthat cushion cells and bind a wide variety of extracellularmolecules■■ Collagen fibers, which provide mechanical strength andresilience■■ Soluble multiadhesive matrix proteins, which bind toand cross-link cell-surface adhesion receptors and otherECM componentsCadherins are cell-adhesion molecules (CAMs) responsible for Ca2-dependent interactions between cells inWe begin our description of the structures and functions ofthese major ECM components in this section, focusing onthe molecular components and organization of the basallamina—the specialized extracellular matrix that helps determine the overall architecture of an epithelial tissue.
In Section 6.4, we extend our discussion to specific ECM moleculesthat are commonly present in nonepithelial tissues.Adherens junctions and desmosomes are cadherincontaining anchoring junctions that bind the membranesof adjacent cells, giving strength and rigidity to the entiretissue. Hemidesmosomes are integrin-containing anchoringjunctions that attach cells to elements of the underlying extracellular matrix.■210CHAPTER 6 • Integrating Cells into Tissues(a)(b)CytosolBasal surfacePlasmamembraneBasallaminaConnectivetissueBasal laminaCell-surfacereceptor proteinsCollagen fibers▲ EXPERIMENTAL FIGURE 6-12 The basal laminaseparates epithelial cells and some other cells fromconnective tissue.
(a) Transmission electron micrograph of a thinsection of cells (top) and underlying connective tissue (bottom).The electron-dense layer of the basal lamina can be seen tofollow the undulation of the basal surface of the cells.(b) Electron micrograph of a quick-freeze deep-etch preparation ofskeletal muscle showing the relation of the plasma membrane,basal lamina, and surrounding connective tissue.
In thispreparation, the basal lamina is revealed as a meshwork offilamentous proteins that associate with the plasma membraneand the thicker collagen fibers of the connective tissue. [Part (a)The Basal Lamina Provides a Foundationfor Epithelial Sheets6-4). The basal lamina is structured differently in differenttissues. In columnar and other epithelia (e.g., intestinallining, skin), it is a foundation on which only one surfaceof the cells rests.
In other tissues, such as muscle or fat,the basal lamina surrounds each cell. Basal laminae play important roles in regeneration after tissue damage and in embryonic development. For instance, the basal lamina helpsIn animals, epithelia and most organized groups of cells areunderlain or surrounded by the basal lamina, a sheetlikemeshwork of ECM components usually no more than60–120 nm thick (Figure 6-12; see also Figures 6-1 andcourtesy of P. FitzGerald. Part (b) from D.
W. Fawcett, 1981, The Cell,2d ed., Saunders/Photo Researchers; courtesy of John Heuser.] FIGURE 6-13 Major components ofthe basal lamina. Schematic model of basallamina showing the organization of themajor protein components. Type IV collagenand laminin each form two-dimensionalnetworks, which are cross-linked by entactinand perlecan molecules. [Adapted fromB. Alberts et al., 1994, Molecular Biology of theCell, 3d ed., Garland, p.
991.]Type IV collagenLamininEntactinPerlecan6.3 • The Extracellular Matrix of Epithelial Sheetsfour- and eight-celled embryos adhere together in a ball. Inthe development of the nervous system, neurons migratealong ECM pathways that contain basal lamina components.Thus the basal lamina is important not only for organizingcells into tissues but also for tissue repair and for guiding migrating cells during tissue formation.Most of the ECM components in the basal lamina aresynthesized by the cells that rest on it. Four ubiquitous protein components are found in basal laminae (Figure 6-13):211(a)(b)Type IV collagen, trimeric molecules with both rodlikeand globular domains that form a two-dimensionalnetwork■Laminins, a family of multiadhesive proteins that forma fibrous two-dimensional network with type IV collagenand that also bind to integrins■Entactin (also called nidogen), a rodlike molecule thatcross-links type IV collagen and laminin and helpsincorporate other components into the ECM■Perlecan, a large multidomain proteoglycan thatbinds to and cross-links many ECM components andcell-surface molecules■As depicted in Figure 6-1, one side of the basal lamina islinked to cells by adhesion receptors, including 64 integrinthat binds to laminin in the basal lamina.
The other side ofthe basal lamina is anchored to the adjacent connective tissueby a layer of fibers of collagen embedded in a proteoglycanrich matrix. In stratified squamous epithelia (e.g., skin), thislinkage is mediated by anchoring fibrils of type VII collagen.Together, the basal lamina and this collagen-containing layer(see the micrograph on page 197) form the structure calledthe basement membrane.Sheet-Forming Type IV Collagen Is a MajorStructural Component in Basal LaminaeType IV collagen, the principal component of all basal lamina, is one of more than 20 types of collagen that participatein the formation of the extracellular matrix in various tissues. Although they differ in certain structural features andtissue distribution, all collagens are trimeric proteins madefrom three polypeptides called collagen chains.
All three chains can be identical (homotrimeric) or different (heterotrimeric). A trimeric collagen molecule contains one ormore three-stranded segments, each with a similar triplehelical structure (Figure 6-14a). Each strand contributed byone of the chains is twisted into a left-handed helix, andthree such strands from the three chains wrap around eachother to form a right-handed triple helix.The collagen triple helix can form because of an unusual abundance of three amino acids: glycine, proline,and a modified form of proline called hydroxyproline(see Figure 3-12). They make up the characteristic repeating motif Gly-X-Y, where X and Y can be any amino▲ FIGURE 6-14 The collagen triple helix.
(a) (Left ) Side viewof the crystal structure of a polypeptide fragment whosesequence is based on repeating sets of three amino acids, Gly-XY, characteristic of collagen chains. (Center ) Each chain istwisted into a left-handed helix, and three chains wrap aroundeach other to form a right-handed triple helix. The schematicmodel (right) clearly illustrates the triple helical nature of thestructure. (b) View down the axis of the triple helix.
The protonside chains of the glycine residues (orange) point into the verynarrow space between the polypeptide chains in the center ofthe triple helix. In mutations in collagen in which other aminoacids replace glycine, the proton in glycine is replaced by largergroups that disrupt the packing of the chains and destablize thetriple-helical structure.
[Adapted from R. Z. Kramer et al., 2001, J. Mol.Biol. 311(1):131.]acid but are often proline and hydroxyproline and lessoften lysine and hydroxylysine. Glycine is essential because its small side chain, a hydrogen atom, is the onlyone that can fit into the crowded center of the threestranded helix (Figure 6-14b). Hydrogen bonds help holdthe three chains together. Although the rigid peptidylproline and peptidyl-hydroxyproline linkages are notcompatible with formation of a classic single-stranded helix, they stabilize the distinctive three-stranded collagen helix.
The hydroxyl group in hydroxyproline helpshold its ring in a conformation that stabilizes the threestranded helix.The unique properties of each type of collagen are duemainly to differences in (1) the number and lengths of thecollagenous, triple-helical segments; (2) the segments thatflank or interrupt the triple-helical segments and that foldinto other kinds of three-dimensional structures; and (3) thecovalent modification of the chains (e.g., hydroxylation,glycosylation, oxidation, cross-linking).
For example, thechains in type IV collagen, which is unique to basal laminae,are designated IV chains. Mammals express six homologous IV chains, which assemble into a series of type IV212CHAPTER 6 • Integrating Cells into Tissues(a)NonhelicalTriple helicalN-terminalglobulardomainC-terminalglobulardomainCollagen IV monomerAssociationcollagens with distinct properties. All subtypes of type IVcollagen, however, form a 400-nm-long triple helix that is interrupted about 24 times with nonhelical segments andflanked by large globular domains at the C-termini of thechains and smaller globular domains at the N-termini.
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