H. Lodish - Molecular Cell Biology (5ed, Freeman, 2003) (796244), страница 96
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❚229Gap Junctions Composed of Connexins AllowSmall Molecules to Pass Between Adjacent CellsEarly electron micrographs of virtually all animal cells thatwere in contact revealed sites of cell–cell contact with a characteristic intercellular gap (Figure 6-31a). This featureprompted early morphologists to call these regions gap junctions. In retrospect, the most important feature of these junctions is not the gap itself but a well-defined set of cylindricalparticles that cross the gap and compose pores connectingthe cytoplasms of adjacent cells—hence their alternate nameof intercytoplasmic junctions.
In epithelia, gap junctions aredistributed along the lateral surfaces of adjacent cells (seeFigures 6-1 and 6-5).In many tissues (e.g., the liver), large numbers of individual cylindrical particles cluster together in patches. This property has enabled researchers to separate gap junctions fromother components of the plasma membrane. When theplasma membrane is purified and then sheared into smallfragments, some pieces mainly containing patches of gapjunctions are generated. Owing to their relatively high protein content, these fragments have a higher density than thatof the bulk of the plasma membrane and can be purified onan equilibrium density gradient (see Figure 5-37).
When these(a)(b)Gapjunction50 nm50 nm▲ EXPERIMENTAL FIGURE 6-31 Gap junctions have acharacteristic appearance in electron micrographs. (a) In thisthin section through a gap junction connecting two mouse livercells, the two plasma membranes are closely associated for adistance of several hundred nanometers, separated by a “gap”of 2–3 nm. (b) Numerous roughly hexagonal particles are visiblein this perpendicular view of the cytosolic face of a region ofplasma membrane enriched in gap junctions.
Each particle alignswith a similar particle on an adjacent cell, forming a channelconnecting the two cells. [Part (a) courtesy of D. Goodenough. Part (b)courtesy of N. Gilula.]230CHAPTER 6 • Integrating Cells into Tissuespreparations are viewed in cross section, the gap junctionsappear as arrays of hexagonal particles that enclose waterfilled channels (Figure 6-31b). Such pure preparations of gapjunctions have permitted the detailed biophysical and functional analysis of these structures.The effective pore size of gap junctions can be measuredby injecting a cell with a fluorescent dye covalently linkedto molecules of various sizes and observing with a fluorescence microscope whether the dye passes into neighboringcells.
Gap junctions between mammalian cells permit thepassage of molecules as large as 1.2 nm in diameter. In insects, these junctions are permeable to molecules as large as2 nm in diameter. Generally speaking, molecules smaller than1200 Da pass freely, and those larger than 2000 Da do notpass; the passage of intermediate-sized molecules is variableand limited. Thus ions, many low-molecular-weight precursors of cellular macromolecules, products of intermediarymetabolism, and small intracellular signaling molecules canpass from cell to cell through gap junctions.In nervous tissue, some neurons are connected by gapjunctions through which ions pass rapidly, thereby allowing very rapid transmission of electrical signals. Impulsetransmission through these connections, called electricalsynapses, is almost a thousandfold as rapid as at chemicalsynapses (Chapter 7).
Gap junctions are also present inmany non-neuronal tissues where they help to integrate the FIGURE 6-32 Molecular structure ofgap junctions. (a) Schematic model of agap junction, which comprises a cluster ofchannels between two plasma membranesseparated by a gap of about 2–3 nm. Bothmembranes contain connexonhemichannels, cylinders of six dumbbellshaped connexin molecules. Twoconnexons join in the gap between thecells to form a gap-junction channel,1.5–2.0 nm in diameter, that connects thecytosols of the two cells. (b) Electrondensity of a recombinant gap-junctionchannel determined by electroncrystallography.
Shown here are side viewsof the complete structure (top) and thesame structure with several chainsremoved to show the channel’s interior(center); on the bottom are perpendicularcross sections through the gap junctionwithin and between the membranebilayers. There appear to be 24transmembrane helices per connexonhemichannel, consistent with each of thesix connexin subunits having four helices.The narrowest part of the channel is ≈1.5 nmin diameter. M membrane bilayer; E extracellular gap; C cytosol. [Part (b) fromV. M.
Unger et al., 1999, Science 283:1176.]electrical and metabolic activities of many cells. In the heart,for instance, gap junctions rapidly pass ionic signals amongmuscle cells and thus contribute to the electrically stimulated coordinate contraction of cardiac muscle cells during abeat. As discussed in Chapter 13, some extracellular hormonal signals induce the production or release of small intracellular signaling molecules called second messengers(e.g., cyclic AMP and Ca2) that regulate cellular metabolism. Because second messengers can be transferred betweencells through gap junctions, hormonal stimulation of onecell can trigger a coordinated response by that same cell andmany of its neighbors. Such gap junction–mediated signaling plays an important role, for example, in the secretionof digestive enzymes by the pancreas and in the coordinatedmuscular contractile waves (peristalsis) in the intestine.
Another vivid example of gap junction–mediated transport isthe phenomenon of metabolic coupling, or metabolic cooperation, in which a cell transfers nutrients or intermediarymetabolites to a neighboring cell that is itself unable to synthesize them. Gap junctions play critical roles in the development of egg cells in the ovary by mediating the movementof both metabolites and signaling molecules between anoocyte and its surrounding granulosa cells as well as between neighboring granulosa cells.A current model of the structure of the gap junction isshown in Figure 6-32.
Vertebrate gap junctions are composed(a)(b)CMEMCConnexonhemichannelGapjunctionchannel2 nmCytosolIntercellular gap6.6 • Plant Tissuesof connexins, a family of structurally related transmembraneproteins with molecular weights between 26,000 and 60,000.A completely different family of proteins, the innexins, formsthe gap junctions in invertebrates. Each vertebrate hexagonal particle consists of 12 connexin molecules: 6 of the molecules are arranged in a connexon hemichannel—a hexagonalcylinder in one plasma membrane—and joined to a connexonhemichannel in the adjacent cell membrane, forming the continuous aqueous channel between the cells. Each connexinmolecule spans the plasma membrane four times; one conserved transmembrane helix from each subunit apparentlylines the aqueous channel.There are probably more than 20 different connexingenes in vertebrates, and different sets of connexins are expressed in different cell types.
Some cells express a single connexin; consequently their gap-junction channels arehomotypic, consisting of identical connexons. Most cells,however, express at least two connexins; these different proteins assemble into hetero-oligomeric connexons, which inturn form heterotypic gap-junction channels. This diversityin channel composition leads to differences in the permeability of channels to various molecules. For example, channelsmade from a 43-kDa connexin isoform, Cx43, are more thana hundredfold as permeable to ADP and ATP as those madefrom Cx32 (32 kDa).
Moreover, the permeability of gapjunctions can be altered by changes in the intracellular pHand Ca2 concentration, as well as by the phosphorylationof connexin, providing numerous mechanisms for regulating transport through them.The generation of mutant mice with inactivating mutations in connexin genes has highlighted the importance ofconnexins in a wide variety of cellular systems. For instance,Cx43-defective mice exhibit numerous defects including defective oocyte maturation due to decreased gap-junctionalcommunication between granulosa cells in the ovary.Mutations in several connexin genes are related tohuman diseases, including neurosensory deafness(Cx26 and Cx31), cataract or heart malformations(Cx43, Cx46, and Cx50), and the X-linked form of CharcotMarie-Tooth disease (Cx32), which is marked by progressivedegeneration of peripheral nerves.
❚KEY CONCEPTS OF SECTION 6.5Adhesive Interactions and Nonepithelial CellsMany nonepithelial cells have integrin-containing aggregates (e.g., focal adhesions, 3D adhesions, podosomes) thatphysically and functionally connect cells to the extracellular matrix and facilitate inside-out and outside-in signaling.■Integrins exist in two conformations that differ in theaffinity for ligands and interactions with cytosolic adapterproteins (see Figure 6-28).■231Dystroglycan, an adhesion receptor expressed by musclecells, forms a large complex with dystrophin, other adapterproteins, and signaling molecules (see Figure 6-29). Thiscomplex links the actin cytoskeleton to the surrounding matrix, providing mechanical stability to muscle.
Mutations invarious components of this complex cause different typesof muscular dystrophy.■Neural cell-adhesion molecules (CAMs), which belongto the immunoglobulin (Ig) family of CAMs, mediateCa2-independent cell–cell adhesion, predominantly inneural tissue and muscle.■The combinatorial and sequential interaction of severaltypes of CAMs (e.g., selectins, integrins, and ICAMs) is critical for the specific and tight adhesion of different types ofleukocytes to endothelial cells in response to local signalsinduced by infection or inflammation (see Figure 6-30).■Gap junctions are constructed of multiple copies of connexin proteins, assembled into a transmembrane channelthat interconnects the cytoplasm of two adjacent cells (seeFigure 6-32). Small molecules and ions can pass throughgap junctions, permitting metabolic and electrical couplingof adjacent cells.■6.6 Plant TissuesWe turn now to the assembly of plant cells into tissues.
The overall structural organization of plantsis generally simpler than that of animals. For instance, plants have only four broad types of cells, which inmature plants form four basic classes of tissue: dermal tissue interacts with the environment; vascular tissue transportswater and dissolved substances (e.g., sugars, ions); spacefilling ground tissue constitutes the major sites ofmetabolism; and sporogenous tissue forms the reproductiveorgans. Plant tissues are organized into just four main organsystems: stems have support and transport functions; rootsprovide anchorage and absorb and store nutrients; leaves arethe sites of photosynthesis; and flowers enclose the reproductive structures.
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