1、1. Integrating Cells into Tissues2. Cell-cell;3. Cell-Matrix ; 4. Extracellular matrix: Components and Functions;5. Cell Walls,Cell junction, Cell adhension Extracellular matrix,Cell junction,Simplified drawing of a cross-section through part of the wall of the intestine.This long, tubelike organ is
2、 constructed from epithelial tissues (red), connective tissues (green), and muscle tissues (yellow). Each tissue is an organized assembly of cells held together between cell-cell, extracellular matrix, or both.,The role of tight junctions in transcellular transport.Transport proteins are confined to
3、 different regions of the plasma membrane in epithelial cells of the small intestine. This segregation permits a vectorial transfer of nutrients across the epithelial sheet from the gut lumen to the blood. In the example shown, glucose is actively transported into the cell by Na+-driven glucose symp
4、orts at the apical surface, and it diffuses out of the cell by facilitated diffusion mediated by glucose carriers in the basolateral membrane. Tight junctions are thought to confine the transport proteins to their appropriate membrane domains by acting as diffusion barriers within the lipid bilayer
5、of the plasma membrane; these junctions also block the backflow of glucose from the basal side of the epithelium into the gut lumen.,Tight junctions,Tight junctions allow cell sheets to serve as barriers to solute diffusion.(A) Schematic drawing showing how a small extracellular tracer molecule adde
6、d on one side of an epithelial cell sheet cannot traverse the tight junctions that seal adjacent cells together. (B) Electron micrographs of cells in an epithelium where a small, extracellular, electron-dense tracer molecule has been added to either the apical side (on the left) or the basolateral s
7、ide (on the right); in both cases the tracer is stopped by the tight junction. (B, courtesy of Daniel Friend.),Structure of a tight junction between epithelial cells of the small intestine.The junctions are shown schematically in (A) and in freeze-fracture (B) and conventional (C) electron micrograp
8、hs. Note that the cells are oriented with their apical ends down. In (B) the plane of the micrograph is parallel to the plane of the membrane, and the tight junction appears as a beltlike band of anastomosing sealing strands that encircle each cell in the sheet. The sealing strands are seen as ridge
9、s of intramembrane particles on the cytoplasmic fracture face of the membrane (the P face) or as complementary grooves on the external face of the membrane (the E face) (see Figure 19-5). In (C) the junction is seen as a series of focal connections between the outer leaflets of the two interacting p
10、lasma membranes, each connection corresponding to a sealing strand in cross-section. (B and C, from N.B. Gilula, in Cell Communication R.P. Cox, ed., pp. 1-29),A current model of a tight junction.It is postulated that the sealing strands that hold adjacent plasma membranes together are formed by con
11、tinuous strands of transmembrane junctional proteins, which make contact across the intercellular space and create a seal. In this schematic the cytoplasmic half of one membrane has been peeled back by the artist to expose the protein strands. Two peripheral proteins associated with the cytoplasmic
12、side of tight junctions have been characterized, but the putative transmembrane protein has not yet been identified. In freeze-fracture electron microscopy the tight-junction proteins would remain with the cytoplasmic (P face) half of the lipid bilayer to give the pattern of intramembrane particles
13、seen in Figure 19-4B, instead of staying in the other half as shown here.,Anchoring junctions,Construction of an anchoring junction.Highly schematized drawing showing the two classes of proteins that constitute such a junction: intracellular attachment proteins and transmembrane linker proteins.,Des
14、mosomes.(A) An electron micrograph of three desmosomes between two epithelial cells in the intestine of a rat. (B) An electron micrograph of a single desmosome between two epidermal cells in a developing newt, showing clearly the attachment of intermediate filaments. (C) A schematic drawing of a des
15、mosome. On the cytoplasmic surface of each interacting plasma membrane is a dense plaque composed of a mixture of intracellular attachment proteins (including plakoglobin and desmoplakins). Each plaque is associated with a thick network of keratin filaments, which are attached to the surface of the
16、plaque. Transmembrane linker proteins, which belong to the cadherin family of cell-cell adhesion molecules, bind to the plaques and interact through their extracellular domains to hold the adjacent membranes together by a Ca2+-dependent mechanism. (A, from N.B. Gilula, in Cell Communication, pp. 1-2
17、9; B, from D.E. Kelly, JCB. 28:51-59),Desmosomes,The distribution of desmosomes and hemidesmosomes in epithelial cells of the small intestine.The keratin filament networks of adjacent cells are indirectly connected to one another through desmosomes and to the basal lamina through hemidesmosomes by i
18、ntegrin.,Hemidesmosomes,Adhesion belts between epithelial cells in the small intestine. This beltlike anchoring junction encircles each of the interacting cells. Its most obvious feature is a contractile bundle of actin filaments running along the cytoplasmic surface of the junctional plasma membran
19、e. The actin filaments are joined from cell to cell by transmembrane linker proteins (cadherins), whose extracellular domain binds to the extracellular domain of an identical cadherin molecule on the adjacent cell.,Adhesion belts,The folding of an epithelial sheet to form an epithelial tube.It is th
20、ought that the oriented contraction of the bundle of actin filaments running along adhesion belts causes the epithelial cells to narrow at their apex and that this plays an important part in the rolling up of the epithelial sheet into a tube (although cellular rearrangements are also thought to play
21、 an important part). An example is the formation of the neural tube in early vertebrate development,Focal adhesion,Determining the size of a gap-junction channel.When fluorescent molecules of various sizes are injected into one of two cells coupled by gap junctions, molecules smaller than about 1000
22、 daltons can pass into the other cell but larger molecules cannot.,Communicating junctions,gap-junction channel,A model of a gap junction.The drawing shows the interacting plasma membranes of two adjacent cells. The apposed lipid bilayers (red) are penetrated by protein assemblies called connexons (
23、green), each of which is thought to be formed by six identical protein subunits (called connexins). Two connexons join across the intercellular gap to form a continuous aqueous channel connecting the two cells.,Gap junctions as seen in the electron microscope.Thin-section (A) and freeze-fracture (B)
24、 electron micrographs of a large and a small gap junction between fibroblasts in culture. In (B) each gap junction is seen as a cluster of homogeneous intramembrane particles associated exclusively with the cytoplasmic fracture face (P face) of the plasma membrane. (From N.B. Gilula, in Cell Communi
25、cation R.P. Cox, ed., pp. 1-29),Three classes of channel proteins.The postulated relationship between the number of protein subunits and pore diameter. (Adapted from B. Hille, Ionic Channels of Excitable Membranes, 2nd ed. Sunderland, MA: Sinauer, 1992.),A proposed model for how gap-junction channel
26、s may close in response to a rise in Ca2+ or a fall in pH in the cytosol.A small rotation of each subunit closes the channel. The model is based on an image analysis of electron micrographs of rapidly frozen tissue in which the structure of gap junction channels in their presumed open state was comp
27、ared with their structure in a Ca2+-induced closed state. It is possible that a similar mechanism operates in the opening and closing of the gated ion channels discussed in Chapter 11. (After P.N.T. Unwin and P.D. Ennis, Nature 307:609-613),synapse,Summary of the various cell junctions found in anim
28、al cell epithelia.This drawing is based on epithelial cells of the small intestine.,Plasmodesmata.(A) The cytoplasmic channels of plasmodesmata pierce the plant cell wall and connect all cells in a plant together. (B) Each plasmodesma is lined with plasma membrane common to two connected cells. It u
29、sually also contains a fine tubular structure (20-40nm), the desmotubule, derived from smooth endoplasmic reticulum.,Plasmodesmata,Plasmodesmata as seen in the electron microscope.(A) Longitudinal section of a plasmodesma from a water fern. The plasma membrane lines the pore and is continuous from o
30、ne cell to the next. Endoplasmic reticulum and its association with the central desmotubule can be seen. (B) A similar plasmodesma in cross-section. (Courtesy of R. Overall.),Cell Adhension,Organ-specific adhesion of dissociated vertebrate embryo cells determined by a radioactive cell-binding assay.
31、The rate of cell adhesion can be measured by determining the number of radioactively labeled cells bound to the cell aggregates after various periods of time. The rate of adhesion is greater between cells of the same kind. In a commonly used modification of this assay, cells labeled with a fluoresce
32、nt or radioactive marker are allowed to bind to a monolayer of unlabeled cells in culture.,Note that the integrins and cadherins are involved in both nonjunctional and junctional cell-cell (cadherins) and cell-matrix (integrins) contacts. The cadherins generally mediate homophilic interactions, wher
33、eas the integrins mediate heterophilic interactions. Both the cadherins and integrins act as transmembrane linkers and depend on extracellular divalent cations to function; for this reason, most cell-cell and cell-matrix contacts are divalent-cation-dependent. The selectins and integrins can also ac
34、t as heterophilic cell-cell adhesion molecules.,Importance of the cytoskeleton This drawing illustrates why cell-adhesion molecules must be linked to the cytoskeleton in order to mediate robust cell-cell or cell-matrix adhesion. In reality, many adhesion proteins would probably be pulled from the ce
35、ll with bits of attached membrane, and the holes left in the membrane would immediately reseal.,Schematic drawing of a typical cadherin molecule.The extracellular part of the protein is folded into five similar domains, four of which contain Ca2+-binding sites. The extracellular domain farthest from
36、 the membrane is thought to mediate cell-cell adhesion; the sequence His-Ala-Val in this domain seems to be involved, as peptides with this sequence inhibit cadherin-mediated adhesion. The cytoplasmic tail interacts with the actin cytoskeleton via a number of intracellular attachment proteins, inclu
37、ding three catenin proteins. a-catenin is structurally related to vinculin. X represents uncharacterized attachment proteins involved in coupling cadherins to actin filaments.,Cadherin,Ca2+,Distribution of E- and N-cadherin in the developing nervous system.Immuno-fluorescence micrographs of a cross-
38、section of a chick embryo showing the developing neural tube labeled with antibodies against E-cadherin (A) and N-cadherin (B). Note that the overlying ectoderm cells express only E-cadherin, while the cells in the neural tube have lost E-cadherin and have acquired N-cadherin. (Courtesy of Kohei Hat
39、ta and Masatoshi Takeichi.),The protein-carbohydrate interaction of inflammation(A) .The lectin domain of P-selectin binds to the specific oligosaccharide shown in (B), which is present on both cell-surface glycoprotein and glycolipid molecules. The lectin domain of the selectins is homologous to le
40、ctin domains found on many other carbohydrate-binding proteins in animals; because the binding to their specific sugar ligand requires extracellular Ca2+, they are called C-type lectins. A three-dimensional structure of one of these lectin domains, determined by x-ray crystallography, is shown in (C
41、); its bound sugar is colored blue. Gal = galactose; GlcNAc = N-acetylglucosamine; Fuc = fucose; NANA = sialic acid.,Selectin,IgSF,Four forms of NCAM of IgSF.The extracellular part of the polypeptide chain in each case is folded into five immunoglobulinlike domains. Disulfide bonds (shown in red) co
42、nnect the ends of each loop forming each Ig-like domain.,IgSF,Integrin,表153,Integrin,* RGD:(ArgGlyAsp),Cells can regulate the activity of their integrins.In (A) cell activation leads to a change in the extracellular binding site of the integrin so that it can now mediate cell adhesion. In (B) the ty
43、rosine phosphorylation of the cytoplasmic tail of the integrins impairs their ability to bind to the actin cytoskeleton. As integrins must bind to the cytoskeleton to mediate robust cell-matrix adhesion, the phosphorylation causes the integrins to relax their grip on the extracellular matrix.,作 业,举例
44、说明细胞粘着的几种类型,Extracellular Matrix,Cells surrounded by spaces filled with extracellular matrix.The particular cells shown in this low-power electron micrograph are those in an embryonic chick limb bud. The cells have not yet acquired their specialized characteristics. (Courtesy of Cheryll Tickle.),The
45、 connective tissue underlying an epithelial cell sheet.It consists largely of extracellular matrix that is secreted by the fibroblasts.,Scanning electron micrograph of fibroblasts in connective tissue.The extracellular matrix surroun-ding the fibroblasts is composed largely of collagen fibrils. The
46、glycoproteins, glycosaminoglycans, and proteoglycans, which normally form a hydrated gel filling the interstices of the fibrous network, have been removed by enzyme and acid treatment. (T. Nishida et al. Invest. Ophthalmol. Vis. Sci. 29:1887-1890),How the extracellular matrix could propagate order f
47、rom cell to cell within a tissue.For simplicity, the figure represents a hypothetical scheme in which one cell influences the orientation of its neighboring cells. It is more likely, however, that the cells would mutually affect one anothers orientation.,The shaping of the extracellular matrix by ce
48、lls.This micrograph shows a region between two pieces of embryonic chick heart (rich in fibroblasts as well as heart muscle cells) that has grown in culture on a collagen gel for four days. A dense tract of aligned collagen fibers has formed between the explants, presumably as a result of the fibrob
49、lasts in the explants tugging on the collagen. (D. Stopak and A.K. Harris, Dev. Biol. 90:383-398),GlycosaminoglycanProteoglycanCollagenElastinLamininFibronectinBasal lamina,Extracellular Matrix,The repeating disaccharide sequence of a dermatan sulfate glycosaminoglycan (GAG) chain.These chains are typically 70 to 200 sugar residues long. There is a high density of negative charges along the chain resulting from the presence of both carboxyl and sulfate groups.,
