細(xì)胞生物學(xué)15

1、 細(xì)胞連接細(xì)胞連接 細(xì)胞黏著及其分子基礎(chǔ)細(xì)胞黏著及其分子基礎(chǔ) 細(xì)胞外基質(zhì)細(xì)胞外基質(zhì)作業(yè)作業(yè) 細(xì)胞連接的功能分類細(xì)胞連接的功能分類 細(xì)胞表面的粘連分子細(xì)胞表面的粘連分子 封閉連接封閉連接 (occluding junctions) 錨定連接錨定連接 (anchoring junctions) 通訊連接通訊連接 (communicating junctions) 緊密連接緊密連接 (tight junction) 緊密連接的緊密連接的結(jié)構(gòu)結(jié)構(gòu)； 緊密連接的功能緊密連接的功能 緊密連接嵴線中的兩類蛋白緊密連接嵴線中的兩類蛋白形成滲漏屏障，起重要的形成滲漏屏障，起重要的封閉作用封閉作用；隔離作用，使游

2、離端與基底面質(zhì)膜上的膜蛋白行隔離作用，使游離端與基底面質(zhì)膜上的膜蛋白行使各自不同的膜功能；使各自不同的膜功能；支持功能。支持功能。 是封閉連接的主要是封閉連接的主要形式，存在于上皮細(xì)胞之間；形式，存在于上皮細(xì)胞之間；封閉蛋白封閉蛋白(occludin)，跨膜四次的膜蛋白，跨膜四次的膜蛋白 (60KD)；claudin 蛋白家族（現(xiàn)已發(fā)現(xiàn)蛋白家族（現(xiàn)已發(fā)現(xiàn) 有有15 種以上）。種以上）。Experimental Evidence Demonstrating that tightJunctions Create a Permeability Barrier. (a) When an electro

3、n-opaque tracer is added to the extra-cellular space on one side of an epithelial cell layer, tracer molecules penetrate into the space between adjacent cells only to the point where they encounter a tight junction. (b) Because the tracer molecules are electron-opaque, their penetration into the int

4、er-cellular space can be visualizedby electron microscopy (TEM).錨定連接在組織內(nèi)分布很廣泛，錨定連接在組織內(nèi)分布很廣泛，在上皮組織，心肌和子宮頸等組織中在上皮組織，心肌和子宮頸等組織中含量尤為豐富；含量尤為豐富； 錨定連接的類型、結(jié)構(gòu)與功能；錨定連接的類型、結(jié)構(gòu)與功能； 錨定連接的錨定連接的結(jié)構(gòu)結(jié)構(gòu)組成。組成。橋粒：橋粒：鉚接相鄰細(xì)胞，提供細(xì)胞內(nèi)中間纖維的錨定位點(diǎn)，鉚接相鄰細(xì)胞，提供細(xì)胞內(nèi)中間纖維的錨定位點(diǎn)，形成整體網(wǎng)絡(luò)，起支持和抵抗外界壓力與張力的作用。形成整體網(wǎng)絡(luò)，起支持和抵抗外界壓力與張力的作用。半橋粒：半橋粒：半橋粒與橋粒

5、形態(tài)類似，但功能和化學(xué)組成不同。半橋粒與橋粒形態(tài)類似，但功能和化學(xué)組成不同。它通過細(xì)胞質(zhì)膜上的膜蛋白整合素將上皮細(xì)胞固著在基底它通過細(xì)胞質(zhì)膜上的膜蛋白整合素將上皮細(xì)胞固著在基底膜上，在半橋粒中，中間纖維不是穿過而是終止于半橋粒膜上，在半橋粒中，中間纖維不是穿過而是終止于半橋粒的致密斑內(nèi)。的致密斑內(nèi)。粘合帶：粘合帶：位于緊密連接下方位于緊密連接下方,相鄰細(xì)胞間形成一個(gè)連續(xù)的帶相鄰細(xì)胞間形成一個(gè)連續(xù)的帶狀結(jié)構(gòu)狀結(jié)構(gòu)。間隙約間隙約1520nm,也稱帶狀橋粒也稱帶狀橋粒 (belt desmosome)。粘合斑：粘合斑：細(xì)胞通過肌動(dòng)蛋白纖維和整連蛋白與細(xì)胞外基質(zhì)細(xì)胞通過肌動(dòng)蛋白纖維和整連蛋白與細(xì)胞外基

6、質(zhì)之間的連接方式。之間的連接方式。與中間纖維相連的錨定連接與中間纖維相連的錨定連接與肌動(dòng)蛋白纖維相連的錨定連接與肌動(dòng)蛋白纖維相連的錨定連接The structure of a desmosome. (a) Electron micrograph of a desmosome from newt epidermis. (b) Schematic model of the molecular architecture of a desmosome. (a: From Douglas E. Kelly, J. CellBiol. 28:51, 1966; by copyright permissio

7、n of the Rockefeller University Press. ) Desmosome structure. (a) An electron micrograph of a desmosome jointing two cells in the skin of a newt (TEM). (b) A schmatic diagramof a desmosome. The distance between cells in the desmosome region is 25-35nm, about that for a nonjunction region. The desmos

8、omecore between the two membranes is filled with glycoproteins called desmocollins and desmogleins. The plaque on that of the membrane contains proteins called desmoplakins and is linked to the cytoskeleton by tonofilaments, whatintermediate filaments that consist ofkeratin, desmocollins depending o

9、n the celltype. HemidesmosomeStructure. (a)As with a desmosome, each hemidesmosome contains a plaque that is anchored to the cyto-skeleton by tono-filaments. (b) As this electron micrograph illustrates, the external surface of the hemi-desmosome abuts directly on the basal lamina (TEM). Adhesion bel

10、ts in epithelial cells in the small intestine. A contractile bundle of actin filamentsruns along the cytoplasmic surface of the plasmamembrane near the apex of each cell, and these bundles of actin filaments in adjacent cells are linked to one another via cadherin molecules that span the cell membra

11、nes. The structure of an adherens junction. Schematic model for the molecular architecture of a zonula adherens. The cyto-plasmic domain of the cadherin molecule is connected to the actin filaments of the cyto-skeleton by linking proteins, including -Catenin. -Catenin has also been implicatedas a ke

12、y element in a signaling pathway leading from the cell surface to the cell nucleus. It is not yet clear, however, if this signaling pathway can be initiated at an adherens junction, which is the reason why the question mark is included in the figure. Schematic model of the protein-protein interactio

13、ns of a focal adhesion complex. Focal adhesions perform (1) a mechanical-structural function, which is carried out by the actin filaments and associated proteins, and (2) a signaling function, which is carried out by the tyrosine kinases Src andFAK. In the model depicted here, Src phosphorylates FAK

14、, which becomes linked to Grb2-Sos, which activates Ras, which sends signals along the MAP kinase pathway. Signals are presumably transmitted into the nucleus, where they stimulate the transcription of genes involved in cell growth and proliferation. 錨定連接具有兩種不同形式：錨定連接具有兩種不同形式：構(gòu)成錨定連接的蛋白可分成兩類：構(gòu)成錨定連接的蛋

15、白可分成兩類：通過錨定連接將相鄰細(xì)胞的骨架系統(tǒng)或?qū)⒓?xì)胞與基通過錨定連接將相鄰細(xì)胞的骨架系統(tǒng)或?qū)⒓?xì)胞與基質(zhì)相連形成一個(gè)堅(jiān)挺、有序的細(xì)胞群體。質(zhì)相連形成一個(gè)堅(jiān)挺、有序的細(xì)胞群體。與中間纖維相連的錨定連接主要包括橋粒和半橋粒與中間纖維相連的錨定連接主要包括橋粒和半橋粒；與肌動(dòng)蛋白纖維相連的錨定連接主要包括粘合帶與與肌動(dòng)蛋白纖維相連的錨定連接主要包括粘合帶與粘合斑粘合斑。，將特定的細(xì)將特定的細(xì)胞骨架成分（中間纖維或微絲）同連接復(fù)合體結(jié)合胞骨架成分（中間纖維或微絲）同連接復(fù)合體結(jié)合在在一起一起 (desmoplakin)；，其胞其胞內(nèi)的部分與附著蛋白相連，胞外的部分與相鄰細(xì)胞內(nèi)的部分與附著蛋白相連，胞外

16、的部分與相鄰細(xì)胞的跨膜連接糖蛋白相互作用或與胞外基質(zhì)相互作用的跨膜連接糖蛋白相互作用或與胞外基質(zhì)相互作用。細(xì)胞內(nèi)附著蛋白細(xì)胞內(nèi)附著蛋白(attachment proteins)跨膜連接的糖蛋白跨膜連接的糖蛋白(desmoglein, desmocollin) 間隙連接間隙連接 (gap junction) 神經(jīng)細(xì)胞間的化學(xué)突觸神經(jīng)細(xì)胞間的化學(xué)突觸 (chemical synapse) 胞間連絲胞間連絲 (plasmodesmata) 間隙連接間隙連接結(jié)構(gòu)結(jié)構(gòu)； 間隙連接的間隙連接的蛋白成分蛋白成分； 間隙連接的間隙連接的功能功能及其及其調(diào)節(jié)機(jī)制調(diào)節(jié)機(jī)制； 間隙連接的間隙連接的通透性通透性是可以

17、調(diào)節(jié)的。是可以調(diào)節(jié)的。間隙連接處相鄰細(xì)胞質(zhì)膜間的間隙為間隙連接處相鄰細(xì)胞質(zhì)膜間的間隙為23nm ；連接子連接子 (connexon) 是間隙連接的基本是間隙連接的基本單位單位，每個(gè)連接子由個(gè)每個(gè)連接子由個(gè) connexin 分分子組成，連接子中心形成一個(gè)直徑約子組成，連接子中心形成一個(gè)直徑約1.5nm 的孔道；的孔道；連接單位由兩個(gè)連接子對接構(gòu)成。連接單位由兩個(gè)連接子對接構(gòu)成。(a)(b)(c)(d)The structure of a gap junction. (a) Electron micrograph of a section through a gap junction perpe

18、ndicular to the plane of the two adjacent membranes. (b) Schematic model of a gapjunction showing the arrangement of six connexonsubunits to form a connexon,which contains half of the channel that connects the cytoplasm of the two adjoining cells. (c) A high-resolution image based on optical diffrac

19、tion of a negatively stained, isolated membrane containing a plaque of gap junction (as shown in d). The relative dimensions of the annulus and connexon are apparent, as is the hexagonal packing of the units within the plaque. (d) Freeze-fracture replica of a gap junction plaque showing the large nu

20、mbers of connexons. 已分離已分離 20 余種構(gòu)成連接子的蛋白余種構(gòu)成連接子的蛋白，屬同屬同一蛋白家族一蛋白家族，其分子量其分子量 26-60KD 不等；不等；連接子蛋白具有連接子蛋白具有4個(gè)個(gè)-螺旋的跨膜區(qū)，螺旋的跨膜區(qū)，是該蛋白家族最保守的區(qū)域；是該蛋白家族最保守的區(qū)域；連接子蛋白的一級結(jié)構(gòu)都比較保守連接子蛋白的一級結(jié)構(gòu)都比較保守, 并并有相似的抗原性；有相似的抗原性；不同類型細(xì)胞表達(dá)不同的連接子蛋白，不同類型細(xì)胞表達(dá)不同的連接子蛋白，間隙連接的孔徑與調(diào)控機(jī)制有所不同。間隙連接的孔徑與調(diào)控機(jī)制有所不同。 間隙連接在代謝偶聯(lián)中的作用間隙連接在代謝偶聯(lián)中的作用間隙連接在神經(jīng)沖

21、動(dòng)信息傳遞過程中的作用間隙連接在神經(jīng)沖動(dòng)信息傳遞過程中的作用間隙連接在早期胚胎發(fā)育和細(xì)胞分化中的作用間隙連接在早期胚胎發(fā)育和細(xì)胞分化中的作用 電突觸電突觸 (electronic junction) 快速實(shí)現(xiàn)胞間信號通訊；快速實(shí)現(xiàn)胞間信號通訊； 間隙連接調(diào)節(jié)和修飾相互獨(dú)立的神經(jīng)元群的行為；間隙連接調(diào)節(jié)和修飾相互獨(dú)立的神經(jīng)元群的行為；為為胚胎發(fā)育中細(xì)胞間的偶聯(lián)提供信號、物質(zhì)通路，胚胎發(fā)育中細(xì)胞間的偶聯(lián)提供信號、物質(zhì)通路，從而為某一特定細(xì)胞提供它的從而為某一特定細(xì)胞提供它的“位置信息位置信息”，并根據(jù)，并根據(jù)其位置影響其分化；其位置影響其分化；腫瘤細(xì)胞之間的間隙連接明顯減少或消失，間隙聯(lián)腫瘤細(xì)胞之

22、間的間隙連接明顯減少或消失，間隙聯(lián)接類似接類似 “腫瘤抑制因子腫瘤抑制因子”。間隙連接允許小分子代謝物和信號分子通過，是細(xì)間隙連接允許小分子代謝物和信號分子通過，是細(xì)胞間代謝偶聯(lián)的基礎(chǔ)；胞間代謝偶聯(lián)的基礎(chǔ)；代謝偶聯(lián)現(xiàn)象在體外培養(yǎng)細(xì)胞中的證實(shí)；代謝偶聯(lián)現(xiàn)象在體外培養(yǎng)細(xì)胞中的證實(shí)；代謝偶聯(lián)作用在協(xié)調(diào)細(xì)胞群體的生物學(xué)功能方面起代謝偶聯(lián)作用在協(xié)調(diào)細(xì)胞群體的生物學(xué)功能方面起重要作用。重要作用。An Electrical Synapse. (a) In electrical synapses, the presynaptic and postsynaptic neurons are coupled by

23、gap junctions. Gap junctions allow small molecules and ions to pass freely from the cytosol of one cell to the next. Therefore, when an action potential arrives at the presynaptic side of an electric synapse, the depolarization spreads passively, due to the flow of positively charged ions, across th

24、e gap junction. (b) The gap junction is composed of sets of channels. Each channel is made up of six protein subunits called connexins. The entire set of six subunits together is called a connexon. Two connexons, one in the presynaptic membrane and one in the post-synaptic membrane, make up a gap ju

25、nction. 降低胞質(zhì)中的降低胞質(zhì)中的pH值和提高自由值和提高自由Ca2+的濃度都可以使其通透性降低；的濃度都可以使其通透性降低；間隙連接的通透性受兩側(cè)電壓梯度間隙連接的通透性受兩側(cè)電壓梯度的調(diào)控及細(xì)胞外化學(xué)信號的調(diào)控。的調(diào)控及細(xì)胞外化學(xué)信號的調(diào)控。Experimental Evidence for Properties of Gap Junctions. (a) Size limitations of gap junction permeability as determined by fluorescence microscopy following microinjection of

26、fluorescent molecules of two different sizes: 1158 Da (top) and 1925 Da (bottom). (b) Use of a fluorescent dye to determine how changes in the intracellular Ca+ concentration affect the permeability of gap junctions. 化學(xué)連接化學(xué)連接A Chemical Synapse. (a) When a nerve impulse from the presynaptic axon arri

27、ves at the synapse (pink arrow), it causes synaptic vesicles containing neurotransmitter in the synaptic knob to fuse with the presynaptic membrane, releasing their contents into the synaptic cleft. (b) Neurotransmitter molecules diffuse across the cleft from the presynaptic (axonal) membrane to the

28、 postsynaptic (dendritic) membrane, where they bind to specific membrane receptor sites and change the polarization of the membrane, either exciting or inhibiting the next cell. (c) Electron micrograph of a chemical synapse (TEM). 胞間連絲胞間連絲結(jié)構(gòu)結(jié)構(gòu)胞間連絲的功能胞間連絲的功能實(shí)現(xiàn)細(xì)胞間由信號介導(dǎo)的物質(zhì)有擇性的轉(zhuǎn)運(yùn)；實(shí)現(xiàn)細(xì)胞間由信號介導(dǎo)的物質(zhì)有擇性的轉(zhuǎn)運(yùn)；實(shí)現(xiàn)細(xì)

29、胞間的電傳導(dǎo)；實(shí)現(xiàn)細(xì)胞間的電傳導(dǎo)；在發(fā)育過程中，胞間連絲結(jié)構(gòu)的改變可以調(diào)節(jié)在發(fā)育過程中，胞間連絲結(jié)構(gòu)的改變可以調(diào)節(jié)植物細(xì)胞間的物質(zhì)運(yùn)輸。植物細(xì)胞間的物質(zhì)運(yùn)輸。相鄰細(xì)胞質(zhì)膜共同構(gòu)成的直徑相鄰細(xì)胞質(zhì)膜共同構(gòu)成的直徑 2040nm的管狀結(jié)構(gòu)；的管狀結(jié)構(gòu)；Plasmodesmata. A plasmodesmata is a channel through the cell wall between two adjacent plant cells, allowing cytoplasmic exchange between the cells. The plasma membrane of one

30、cell is continuous with that of the outer cell at each plasmodesmata. Most plasmodesmata have a narrow cylindrical desmotubule at the center that is derived from the ER and appears to be continuous with the ER of both cells. Between the desmotubule and the plasma membrane that lines the plasmodesma

31、is a narrow ring of cytoplasm called the annulus. (a) This electron micrograph and diagram show the cell wall between two adjacent root cells of timothy grass, with numerous plasmodesmata (TEM). (b) A diagrammatic view of a cell wall with numerous plasmodesmata, illustrating the continuity of the ER

32、 and cytoplasm between adjacent cells. (c) This electron micrograph shows many plasmodesmata in cross section (TEM). 粘連分子均為整合膜蛋白，在胞內(nèi)與粘連分子均為整合膜蛋白，在胞內(nèi)與細(xì)胞骨架成分相連；細(xì)胞骨架成分相連；多數(shù)要依賴多數(shù)要依賴 Ca2+ 或或 Mg2+ 才起作用。才起作用。 類型類型 粘著方式粘著方式同種類型細(xì)胞間的彼此粘連同種類型細(xì)胞間的彼此粘連是許多組織結(jié)構(gòu)是許多組織結(jié)構(gòu)的基本特征；細(xì)胞與細(xì)胞間的粘連是由特定的細(xì)的基本特征；細(xì)胞與細(xì)胞間的粘連是由特定的細(xì)胞粘連分子

33、所介導(dǎo)的。胞粘連分子所介導(dǎo)的。粘連分子的特征粘連分子的特征粘連分子類型及細(xì)胞間粘著方式粘連分子類型及細(xì)胞間粘著方式Experimental demonstration of cell-cell recognition. When cellsfrom two types of embryonic organs are dissociated and then intermixed, the cells from the two organs aggregate and then sort out by associating with other cells of the same type.

34、The results of two such experiments are shown here. (a) In this experiment,two regions of an early amphibian embryo (the ectoderm and mesoderm) were dissociated into single cells and combined. At first the cells form a mixed aggregate, but eventually they sort out. The ectodermal cells (shown in red

35、) move to the outer surface of the aggregate, which is where they would be located in the embryo, and themesodermal cells (shown in purple) move to the interior, the position they would occupy in the embryo. Both types of cells then differentiate into the types of structures they would normally give

36、 rise to . (b) Light micrograph showing the results of an experiment in which precartilage cells from a chick limb are mixed with chick heart ventricle cells. The two types of cells have sorted themselves out of the mixed aggregate with the heart cells forming a layer on the outside of the precartil

37、age cells. 鈣粘素鈣粘素 (Cadherins) 選擇素選擇素 (Selectin) 免疫球蛋白超家族的免疫球蛋白超家族的 CAM (Ig-Superfamily，IgSF) 整合素整合素 (Integrins) 質(zhì)膜整合蛋白聚糖也介導(dǎo)細(xì)胞間的粘著質(zhì)膜整合蛋白聚糖也介導(dǎo)細(xì)胞間的粘著屬同親性依賴屬同親性依賴Ca2+的細(xì)胞粘連糖蛋白，的細(xì)胞粘連糖蛋白，介導(dǎo)依賴介導(dǎo)依賴Ca2+的細(xì)胞粘著和從的細(xì)胞粘著和從ECM到細(xì)胞到細(xì)胞質(zhì)傳遞信號。對胚胎發(fā)育中的細(xì)胞識別、遷質(zhì)傳遞信號。對胚胎發(fā)育中的細(xì)胞識別、遷移和組織分化以及成體組織器官構(gòu)成具有主移和組織分化以及成體組織器官構(gòu)成具有主要作用。要作用。(

38、30多個(gè)成員的糖蛋白家族多個(gè)成員的糖蛋白家族) E-Cadherins (epithelial) N-Cadherins (neural) P-Cadherins (placental) 橋粒鈣粘素橋粒鈣粘素屬異親性依賴于屬異親性依賴于Ca2+的能與特異糖基的能與特異糖基識別并相結(jié)合的糖蛋白，其胞外部分具有識別并相結(jié)合的糖蛋白，其胞外部分具有凝集素樣結(jié)構(gòu)域凝集素樣結(jié)構(gòu)域 (lectin-like domain)。主要主要參與白細(xì)胞與脈管內(nèi)皮細(xì)胞之間的識別與參與白細(xì)胞與脈管內(nèi)皮細(xì)胞之間的識別與粘著。粘著。 有三種類型的選擇素：有三種類型的選擇素：P (Platelet) 選選擇素?fù)袼?、E (En

39、dothelial) 選擇素和選擇素和 L (Leukocyte) 選擇素。選擇素。 分子結(jié)構(gòu)中具有與免疫球蛋白類似分子結(jié)構(gòu)中具有與免疫球蛋白類似的結(jié)構(gòu)域的的結(jié)構(gòu)域的CAM超家族超家族。介導(dǎo)同親性細(xì)介導(dǎo)同親性細(xì)胞粘著或介導(dǎo)異親性細(xì)胞粘著，但其粘胞粘著或介導(dǎo)異親性細(xì)胞粘著，但其粘著作用不依賴著作用不依賴Ca2+，其中，其中 N-CAMs在神在神經(jīng)組織細(xì)胞間的粘著中起主要作用。經(jīng)組織細(xì)胞間的粘著中起主要作用。 是由是由 和和 兩個(gè)亞基形成的異源二聚兩個(gè)亞基形成的異源二聚體糖蛋白。在人體細(xì)胞中已發(fā)現(xiàn)了體糖蛋白。在人體細(xì)胞中已發(fā)現(xiàn)了16種種 鏈和鏈和8種種 鏈，它們相互配合可形成鏈，它們相互配合可形成

40、 22種不同的二聚體整合素，并可與不同的種不同的二聚體整合素，并可與不同的配基結(jié)合，從而介導(dǎo)細(xì)胞與基質(zhì)、細(xì)胞配基結(jié)合，從而介導(dǎo)細(xì)胞與基質(zhì)、細(xì)胞與細(xì)胞之間的粘著。與細(xì)胞之間的粘著。 細(xì)胞中主要的粘連分子家族；細(xì)胞中主要的粘連分子家族； 與細(xì)胞錨定連接相關(guān)的粘連分子；與細(xì)胞錨定連接相關(guān)的粘連分子； 非錨定連接非錨定連接 (nonjunctional adhesion)的細(xì)胞粘連分子及其作用部位。的細(xì)胞粘連分子及其作用部位。非錨定連接的細(xì)胞間粘著方式示意圖非錨定連接的細(xì)胞間粘著方式示意圖 1. 鈣粘素；鈣粘素； 2. 免疫球蛋白類細(xì)胞粘著分子；免疫球蛋白類細(xì)胞粘著分子； 3. 選擇素；選擇素； 4.

41、 整合素；整合素； 5. 質(zhì)膜整合蛋白聚糖質(zhì)膜整合蛋白聚糖 An overview of the types of interactions involving the cellsurface. Four types of cell-cell adhesive interactions are shown, as well as two types of interactions between cells andextracellular substrate (IF, intermediate filament; AF, actin filament). Keep in mind that

42、the various interactions depictedhere do not occur on a single cell type but are shown in this manner for purposes of illustration. For example, interactionsbetween selectins and lectins occur primarily between circulating leukocytes and the walls of blood vessels.細(xì)胞連接類型細(xì)胞連接類型主要成員主要成員Ca2+或或Mg2+依賴性依賴

43、性胞內(nèi)骨胞內(nèi)骨架成分架成分與細(xì)胞與細(xì)胞連接關(guān)系連接關(guān)系細(xì)胞細(xì)胞與細(xì)與細(xì)胞連胞連接接鈣粘素鈣粘素E、N、P 鈣粘素鈣粘素+Actin纖維纖維粘著帶粘著帶橋粒橋粒-鈣粘素鈣粘素+中間纖維中間纖維橋橋 粒粒選擇素選擇素P 選擇素選擇素+-免疫球蛋白類免疫球蛋白類N 細(xì)胞粘著分子細(xì)胞粘著分子-血細(xì)胞整合素血細(xì)胞整合素 12+Actin纖維纖維-細(xì)胞細(xì)胞與基與基質(zhì)連質(zhì)連接接整合素整合素約約20種類型種類型+Actin纖維纖維粘著斑粘著斑 64+中間纖維中間纖維半橋粒半橋粒質(zhì)膜蛋白聚糖質(zhì)膜蛋白聚糖Syndecans-Actin纖維纖維-細(xì)胞連細(xì)胞連接類型接類型粘連分子粘連分子胞外胞外胞內(nèi)某些胞內(nèi)某些結(jié)合蛋

44、白結(jié)合蛋白細(xì)胞骨細(xì)胞骨架類型架類型細(xì)胞細(xì)胞與細(xì)與細(xì)胞連胞連接接橋橋粒粒鈣粘素鈣粘素desmogleinsdesmocollins相鄰細(xì)胞的鈣粘素相鄰細(xì)胞的鈣粘素 DesmoplakinsPlakoglobin中間纖維中間纖維粘粘著著帶帶鈣粘素鈣粘素（E 鈣粘素）鈣粘素）同同 上上Vinculin Catenin微微 絲絲細(xì)胞細(xì)胞與胞與胞外基外基質(zhì)連質(zhì)連接接半半橋橋粒粒整合素整合素(6 4)胞外基質(zhì)蛋白胞外基質(zhì)蛋白（ 基底膜蛋白）基底膜蛋白）Desmoplakin-like蛋白蛋白中間纖維中間纖維粘粘著著斑斑整合素整合素胞外基質(zhì)蛋白胞外基質(zhì)蛋白TalinVinculin-actinin微微 絲絲

45、非錨定連接的細(xì)胞粘連分子及其作用部位非錨定連接的細(xì)胞粘連分子及其作用部位 (深色深色) 基本概念基本概念 膠原膠原 (collagen) 氨基聚糖和蛋白聚糖氨基聚糖和蛋白聚糖 層粘連蛋白和纖粘連蛋白層粘連蛋白和纖粘連蛋白 彈性蛋白彈性蛋白 (elastin) 植物細(xì)胞壁植物細(xì)胞壁 細(xì)胞外被細(xì)胞外被 (cell coat) 細(xì)胞外基質(zhì)細(xì)胞外基質(zhì) (extracellular matrix) 真核細(xì)胞的細(xì)胞外結(jié)構(gòu)真核細(xì)胞的細(xì)胞外結(jié)構(gòu) (extracellular structures)概念：概念：又稱糖萼又稱糖萼 (glycocalyx)，指在細(xì)胞質(zhì)指在細(xì)胞質(zhì)膜的外表面覆蓋的一層膜的外表面覆蓋的一

46、層粘多糖粘多糖物質(zhì)，實(shí)物質(zhì)，實(shí)際上是指細(xì)胞表面與質(zhì)膜中的蛋白或脂際上是指細(xì)胞表面與質(zhì)膜中的蛋白或脂類分子共價(jià)結(jié)合的寡糖鏈。類分子共價(jià)結(jié)合的寡糖鏈。功能：功能：對膜蛋白起保護(hù)作用，并在細(xì)胞識對膜蛋白起保護(hù)作用，并在細(xì)胞識別中起重要作用。別中起重要作用。 膀胱上皮細(xì)胞表面的糖被，釕紅染色的電鏡超薄切片（梁鳳霞，丁明孝）膀胱上皮細(xì)胞表面的糖被，釕紅染色的電鏡超薄切片（梁鳳霞，丁明孝）概念：概念：主要功能：主要功能：構(gòu)成支持細(xì)胞的框架，負(fù)責(zé)組織的構(gòu)建；構(gòu)成支持細(xì)胞的框架，負(fù)責(zé)組織的構(gòu)建；胞外基質(zhì)三維結(jié)構(gòu)及成份的變化，改變細(xì)胞微胞外基質(zhì)三維結(jié)構(gòu)及成份的變化，改變細(xì)胞微環(huán)境從而對細(xì)胞形態(tài)、生長、分裂、分化

47、和凋環(huán)境從而對細(xì)胞形態(tài)、生長、分裂、分化和凋亡起重要的調(diào)控作用；亡起重要的調(diào)控作用；胞外基質(zhì)的信號功能。胞外基質(zhì)的信號功能。簡稱簡稱ECM，指分布于細(xì)胞外空間，指分布于細(xì)胞外空間, 由細(xì)胞分由細(xì)胞分泌的蛋白和多糖所構(gòu)成的泌的蛋白和多糖所構(gòu)成的網(wǎng)絡(luò)結(jié)構(gòu)網(wǎng)絡(luò)結(jié)構(gòu)。An overview of the macromolecular organization of the extracellular matrix. The proteins and polysaccharides shown in this illustration will be discussed in the following

48、 sections. The proteins depicted (fibronectin,collagen, and laminin) contain binding sites for one another, as well as binding sites for receptors (integrins) that are located at the cell surface. The proteoglycans are huge protein-polysaccharide complexes that occupymuch of the volume of the extrac

49、ellular space. 生物種類生物種類細(xì)胞外結(jié)構(gòu)細(xì)胞外結(jié)構(gòu)結(jié)構(gòu)纖維結(jié)構(gòu)纖維水化基質(zhì)組分水化基質(zhì)組分粘連分子粘連分子動(dòng)物細(xì)胞動(dòng)物細(xì)胞細(xì)胞外基質(zhì)細(xì)胞外基質(zhì) 膠原膠原 彈性蛋白彈性蛋白蛋白聚糖蛋白聚糖纖粘連蛋白纖粘連蛋白層粘連蛋白層粘連蛋白植物細(xì)胞植物細(xì)胞細(xì)胞壁細(xì)胞壁 纖維素纖維素半纖維素半纖維素伸展蛋白伸展蛋白果膠質(zhì)果膠質(zhì)膠原是胞外基質(zhì)最基本結(jié)構(gòu)成份之膠原是胞外基質(zhì)最基本結(jié)構(gòu)成份之一，動(dòng)物體內(nèi)含量最豐富的蛋白（總量一，動(dòng)物體內(nèi)含量最豐富的蛋白（總量的的30以上）。以上）。 膠原類型及其在組織中的分布膠原類型及其在組織中的分布 膠原及其分子結(jié)構(gòu)膠原及其分子結(jié)構(gòu) 膠原的合成與加工膠原的合成與加

50、工 膠原的功能膠原的功能膠原是胞外基質(zhì)中最主要的水不溶性纖維蛋白膠原是胞外基質(zhì)中最主要的水不溶性纖維蛋白；目前已發(fā)現(xiàn)的膠原有目前已發(fā)現(xiàn)的膠原有20多種類型，但了解最多多種類型，但了解最多的是的是I-型型，其中其中I-III 型含量最豐富型含量最豐富，形成類似形成類似的纖維結(jié)構(gòu)的纖維結(jié)構(gòu)；但并非所有膠原都形成纖維；但并非所有膠原都形成纖維；I 型膠原纖維束，主要分布于皮膚、肌腱、韌帶型膠原纖維束，主要分布于皮膚、肌腱、韌帶及骨中，具有很強(qiáng)的抗張強(qiáng)度；及骨中，具有很強(qiáng)的抗張強(qiáng)度；II 型膠原主要存在于軟骨中；型膠原主要存在于軟骨中；III 型膠原形成微細(xì)的原纖維網(wǎng)，廣泛分布于伸展型膠原形成微細(xì)的原

51、纖維網(wǎng)，廣泛分布于伸展性的組織，如疏松結(jié)締組織；性的組織，如疏松結(jié)締組織； 型膠原形成二維網(wǎng)格樣結(jié)構(gòu)，是基膜的主要成型膠原形成二維網(wǎng)格樣結(jié)構(gòu)，是基膜的主要成分及支架。分及支架。膠原纖維的基本結(jié)構(gòu)單位是膠原纖維的基本結(jié)構(gòu)單位是原膠原原膠原；原膠原是由三條肽鏈盤繞成的原膠原是由三條肽鏈盤繞成的三股螺旋三股螺旋結(jié)構(gòu)結(jié)構(gòu)；原膠原肽鏈具有原膠原肽鏈具有Gly-x-y重復(fù)序列，對膠重復(fù)序列，對膠原纖維的高級結(jié)構(gòu)的形成是重要的；原纖維的高級結(jié)構(gòu)的形成是重要的； 在膠原纖維內(nèi)部，原膠原蛋白分子呈在膠原纖維內(nèi)部，原膠原蛋白分子呈1/4交替平行排列，形成周期性橫紋。交替平行排列，形成周期性橫紋。 The Stru

52、cture of the Collagen. (a) Collagen fibers as seen by SEM. (b) A collagen fiber contains many fibrils, each of which is a bundle of collagen molecules, also called tropocollagen. (c) Each collagen molecule is a triple helix consisting of (d) three entwined chains. The repeating bands visible on the

53、fibers in the SEM in part a reflect the regular but offset way in which collagen molecules associate laterally to form fibrils. （a）膠原纖維的分子結(jié)構(gòu)與形成過程）膠原纖維的分子結(jié)構(gòu)與形成過程()； （b）膠原纖維的電鏡照片）膠原纖維的電鏡照片 前原膠原在細(xì)胞外由兩種專一性不同的蛋白前原膠原在細(xì)胞外由兩種專一性不同的蛋白水解酶作用水解酶作用, 分別切去分別切去 N-末端前肽及末端前肽及 C-末端末端前肽，成為原膠原前肽，成為原膠原 (procollagen)；原膠原進(jìn)

54、而聚合裝配成膠原原纖維原膠原進(jìn)而聚合裝配成膠原原纖維 (collagen fibril) 和膠原纖維和膠原纖維 (collagen fiber)。前原膠原前原膠原 (preprocollagen) 是原膠原的前體和分泌是原膠原的前體和分泌形式，形式，在粗面內(nèi)質(zhì)網(wǎng)合成在粗面內(nèi)質(zhì)網(wǎng)合成、加工與組裝加工與組裝，經(jīng)高爾基體分泌經(jīng)高爾基體分泌；前體前體 肽鏈在粗面內(nèi)質(zhì)網(wǎng)合成，并形成前原肽鏈在粗面內(nèi)質(zhì)網(wǎng)合成，并形成前原膠原膠原 (preprocollagen)；膠原在胞外基質(zhì)中含量最高，剛性及抗膠原在胞外基質(zhì)中含量最高，剛性及抗張力強(qiáng)度最大，構(gòu)成細(xì)胞外基質(zhì)的骨架張力強(qiáng)度最大，構(gòu)成細(xì)胞外基質(zhì)的骨架結(jié)構(gòu)，細(xì)胞

55、外基質(zhì)中的其它組分通過與結(jié)構(gòu)，細(xì)胞外基質(zhì)中的其它組分通過與膠原結(jié)合形成結(jié)構(gòu)與功能的復(fù)合體；膠原結(jié)合形成結(jié)構(gòu)與功能的復(fù)合體；在不同組織中，膠原組裝成不同的纖維在不同組織中，膠原組裝成不同的纖維形式，以適應(yīng)特定功能的需要；形式，以適應(yīng)特定功能的需要；膠原可被膠原酶特異降解，而參入胞外膠原可被膠原酶特異降解，而參入胞外基質(zhì)信號傳遞的調(diào)控網(wǎng)絡(luò)中?；|(zhì)信號傳遞的調(diào)控網(wǎng)絡(luò)中。 氨基聚糖氨基聚糖 (glycosaminoglycan, GAGs) 蛋白聚糖蛋白聚糖 (proteoglycan) 氨基聚糖是由重復(fù)的氨基聚糖是由重復(fù)的二糖單位二糖單位構(gòu)成的長鏈多糖，二糖構(gòu)成的長鏈多糖，二糖單位之一是氨基己糖單位

56、之一是氨基己糖（氨基葡萄糖或氨基半乳糖）（氨基葡萄糖或氨基半乳糖） + 糖醛酸糖醛酸;氨基聚糖有透明質(zhì)酸氨基聚糖有透明質(zhì)酸、4-硫酸軟骨素硫酸軟骨素、6-硫酸軟骨素硫酸軟骨素、硫酸皮膚素、硫酸乙酰肝素、肝素和硫酸角質(zhì)素等，硫酸皮膚素、硫酸乙酰肝素、肝素和硫酸角質(zhì)素等，透明質(zhì)酸是增殖細(xì)胞和遷移細(xì)胞的胞外基質(zhì)主要成透明質(zhì)酸是增殖細(xì)胞和遷移細(xì)胞的胞外基質(zhì)主要成分，也是蛋白聚糖的主要結(jié)構(gòu)組分；分，也是蛋白聚糖的主要結(jié)構(gòu)組分；透明質(zhì)酸在結(jié)締組織中起強(qiáng)化、彈性和潤滑作用；透明質(zhì)酸在結(jié)締組織中起強(qiáng)化、彈性和潤滑作用； 透明質(zhì)酸使細(xì)胞保持彼此分離，使細(xì)胞易于運(yùn)動(dòng)遷透明質(zhì)酸使細(xì)胞保持彼此分離，使細(xì)胞易于運(yùn)動(dòng)遷移

57、和增殖并阻止細(xì)胞分化。移和增殖并阻止細(xì)胞分化。其中透明質(zhì)酸其中透明質(zhì)酸 (hyaluronic acid) 及其生物學(xué)功能為及其生物學(xué)功能為The structure of a cartilage-type proteoglycan complex. (a) Schematic representation ofa single proteoglycan consisting of a core protein to whicha large number of glycosaminoglycan chains (GAGs, shown in red) are attached. A prot

58、eoglycan from cartilage matrix (e.g., aggrecan) may contain about 30 keratan sulfate and 100 chondroitin sulfate chains. Proteoglycans found in basement membranes (e.g., perlecan and agrin) have only a few GAG chains attached to the core protein. (b) The structures of the repeating disacchrides that

59、 make up each of the GAGs shown in this figure. All GAGs bear large numbers of negative charges (indicated by the blue shading).(c)Inthe cartilage matrix, individual proteoglycans are linked to a nonsulfated GAG, called hyaluronic acid, to form a giant complex with a molecular mass of about 3,000,00

60、0 daltons. The box indicatesone of the proteoglycans of the type shown in part a. (d) Electron micrograph of a proteoglycan complex, comparable to that illustrated in part c, that was isolated from cartilage matrix. 蛋白聚糖見于所有結(jié)締組織和細(xì)胞外基質(zhì)及許多細(xì)胞蛋白聚糖見于所有結(jié)締組織和細(xì)胞外基質(zhì)及許多細(xì)胞表面；表面；蛋白聚糖蛋白聚糖由氨基聚糖與核心蛋白由氨基聚糖與核心蛋白(cor