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The Inner Life of the Cell
生物 2008-07-13 20:23:03 阅读37 评论0 字号：大中小
The Inner Life of the Cell
While red blood cells are carried away at a high velocity by a strong blood flow,leukocytes roll sowly on endothelial cells.P-selectins on endothelial cells interact with PSGL-1,aglycoprotein on leukocyte microvilli. Leukocytes pushed by the blood flow adhere and roll on endothelial cells because the existing interactions are broken while new ones are formed.These interactions are possible because the extended extracellular domains of both proteins immerge from extracellular matrix,which covers the surface of both cell types.
The outer leaflet of the lipid bilayer is rich in sphingolipid and phosphotidylcholine.Sphingolipid rich raft raised about the rest of the rafts recuse specified membrane proteins.Rafts rigidity caused by the tight packing of cholesterol molecules against the straight sphingolipid hydrocarbon chains.Outside the raft,kinks unsaturated chains and lower cholesterol concentration result in increase fluidity.At sights of information,secreted chemokines bind to heparan sulfate proteoglycan endothelial cells are presented to leukocyte's seven transmembrane receptors. The binding stimulates leukocytes and triggers an intracllular cascade of signaling reactions.
The inner leaflet of the bilayer has very different composition than that of the outer leaflet.While some proteins traverse the membrane,others are rivet anchored into the inner leaflet by covalently attach fatty acid chains or a recruited through non-covalent interactions with membrane proteins.The membrane bond protein complexes are critical for the transmition of signal across the plasma membrane.The leafy lipid bilayer,spectrin tetramers arranged into hexagonal network that are anchored by membrane proteins.This network forms the membrane skeleton that contributes to membrane stability and membrane protein distribution.
The cytososkelecton is comprised of networks of filamental protein that are responsible for the special organization of cytosoltic components.Inside the microvilli,actin filaments form type parallel bundles which are stabilized by cross -linking proteins.While deeper in the cytosol,the actin networks adapt jawlike structure stabilized by a variety of actin binding proteins.Filaments kep their minus-ends by protein complex,grow away from plasma membrane by the addition of actin polymers to the plus-end. The actin network is a very dynamic structure with continuous directional polymerization and disassembly.severing proteins induce kinks in the filaments and led to the formation of short filaments that rapidly depolymerize or give rise to new filaments.
The cytososkeleton includes a network of microtubules created by lateral association of protofilaments formed with the polymerization of tubulin dimers.While the plus-ends of some microtubule extend toward the plasma membrane,protein stabilizes the curve conformation of protofilaments from other microtubules,causing the rapidly plus-end depolymeriztion.
Microtubules provide tracts along which membrane bounded vesicles travel to and from the plasma membrane. The directional movement of these cargo vesicles is due to a family of motor proteins linking vesicles and microtubules. Membrane bounded organelles like mitochondria are loosely trapped by the cytoskeleton.Mitochondria change shape continuously and their orientation is partly dictated by their interaction with microtubules.
All the microtubules originate from the centrosome, a discrete fibrous structure containing two centrioles and located near the cell nucleus. Pores in the nuclear envelope allow the import of particles containing mRNA and proteins into the cytosol.
Here free ribosomes translate the mRNA molecules into proteins. Some of these proteins will reside in the cytosol,others will associate with specialized cytosolic proteins and be imported into mitochondria or other organells.
The synthesis of cell-secreted and integral membrane proteins is initiated by free ribosomes, which then dot to protein translocators on the surface of the endoplasmic reticulum. Nasen()proteins pass through a aqueous pore on the translocator.
Cell secreted proteins accumulate in the lumen of endoplasmic reticulum while integral membrane proteins become embedded in the endoplasmic reticulum membrane.Proteins are transport from the endoplasmic reticulum to the Golgi apparatus(GA) by vesicles travelling along the microtubules.
Protein glycosylation initiated in the endplasmic reticulum is completed inside the lumen of Golgi apparatus.Fully glycosylation proteins are transport from the Golgi apparatus to the plasma membrane.
When the vesicle fuses with plasma membrane,proteins containing in the vesicle lumen are secreted and proteins embedded in the vesicle membrane diffuse in the cell membrane.At sights of information,chemokine secreted by the endothelial cells bind to the extracellular domains of G-protein coupled membrane receptors. This binding causes a conformational change in the cytosonic portion of the receptor,and consequential activation of the subunit of the G-protein. The activation of the G-protein subunit triggers a cascade of protein activation which in turn leads to the activation and clustering of integrin inside lipid rafts.
A domatic conformation change occurs in the extracellular domain of activated integrins.These now allow for they interaction with I-cam proteins display in the surface of the endothelial cells. These strong interactions immobilize the rolling leukocyte at sight of information. Additional signaling events cause profound reorganization of the cytoskeleton,resulting in the spreading of one edge of the leukocyte.The leading edge of the leukocyte inserts itself between the endothelial cells,and leukocytes migrate through the blood vessel walls into the inflamed tissue.Rolling,activation,adhesion,and trans endothelial migration are the four steps of a proeess called leukocyte extravasation.
汉化解说稿
此解说稿根据上面的英文，并对照原视频翻译而成。其中必然存在一些不妥之处，恳请大家批评指正。
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当红细胞被强有力的血流高速运输时，白细胞则在血管壁的内皮细胞上缓慢滚动。内皮细胞上的P-选择蛋白与PSGL-1——一种白细胞上的糖蛋白相结合。白细胞之所以能在血管壁的内皮细胞上滚动，就是因为这种结合的不断破坏与重建。被细胞间质隐没的两种蛋白的标准的胞外结构域，为这种交互式的结合提供了可能，这种细胞间质存在于各种细胞之间。磷脂双分子层的外叶含有丰富的鞘磷脂和磷脂胆碱。鞘磷脂组成的脂筏可以在其周围募集一些特定的膜蛋白。脂筏的刚性有赖于附着在鞘磷脂的直链周围的胆固醇分子。脂筏以外，不饱和烃链的纠缠以及较低的胆固醇浓度导致了流动性的增加。一察觉到信息，由内皮细胞分泌并与硫酸乙酰肝素蛋白多糖（HSPG）结合的趋化激素就被呈递给白细胞的由7个跨膜区构成的受体。这种粘附刺激白细胞并引发了细胞内的级联通讯反应。 磷脂双分子层的内叶在构成上与外叶有很大不同。一些蛋白质横贯质膜，其它则通过共价连接脂肪酸或一个与膜蛋白的非共价作用将自己锚定在内叶上。膜与蛋白的联合体是跨膜信号传递中至关重要的部分。在叶状的磷脂双分子层上，血影蛋白被构建成六边形的网状结构，并被膜蛋白锚定。这种网状结构组成了细胞膜的骨架，增强了细胞膜的稳定性，对膜蛋白的分布也有重要作用。细胞骨架由网状结构的微丝蛋白构成。这些蛋白质是细胞中特殊组织形成的原因。
在细胞的微绒毛的内部，肌动蛋白的丝状结构成了平行的束状纤维，并由横向穿插的蛋白纤维加固。
在细胞质的更深层，肌动蛋白的网络改变成Z字型的结构，并被多种微丝结合蛋白加固。
微丝依靠原肌球调节蛋白蛋稳定其负端，并通过在其正端添加肌动蛋白聚合体向远离质膜的方向生长。肌动蛋白的网络是一个动态的结构，持续不断地进行定向的聚合和解聚。裂解蛋白可以引起微丝的断裂而形成较短小的微丝并迅速解聚或者再聚合成新的微丝。
细胞骨架还包括微管蛋白构成的网络，这种网络由（13条）微管蛋白原纤维体横向联结构成，原纤维则由微管蛋白二聚体头尾相接而成。当某些微管的正端向质膜的方向延伸时，蛋白质在其它微管上保持着各种构象间的平衡，使得它们的正端快速解聚。微管为运往质膜或来自质膜的由膜结构包裹着的运输泡提供运输线路。这些运输泡的方向性移动应归功于一种与运输泡连接的动力蛋白组合和微管。线粒体一类的膜结构细胞器，由细胞骨架宽松地限制着。线粒体不断地改变着它们的外型，并靠其与微管的相互作用部分地改变其方位。所有的微管都发源于中心体。中心体包含有一对分开的具有纤维结构的中心粒，位于细胞核的附近。核膜上的核孔允许少量的信使RNA和某些蛋白质进入细胞质。
这里，游离核糖体#将信使RNA翻译为蛋白质分子。这里制造的蛋白质分子，一些将留在细胞质中，其它的将与特异的细胞质结合蛋白相结合而被引入线粒体和其它细胞器。分泌蛋白和膜内在蛋白质的合成开始于游离的核糖体，随后将停泊在内质网表面的转运蛋白上继续进行。这些蛋白质将通过一个在转运蛋白上的水合的孔。细胞分泌蛋白将在内质网的内腔中聚积，
而膜内在蛋白质将被植入到内质网的膜上。将蛋白质从内质网运输到高尔基体，是由沿着微管运动的运输囊泡实现的。开始于内质网中的蛋白质糖基化在高尔基体中全部完成。完全糖基化的蛋白质分子，将从高尔基体运送到质膜。
当运输泡与质膜结合时，在运输泡内腔中的蛋白质将被分泌，而植入到膜上的蛋白质分子将扩散到细胞膜上。 一察觉到信息，由内皮细胞分泌的趋化激素就与细胞外的G蛋白的跨膜受体结构域结合，这一结合引起了G-蛋白受体构象上的改变，而激活了G蛋白的亚基。G蛋白亚基的激活将引发一个蛋白质的级联反应，最终将按顺序导致整联蛋白的活化和其在脂筏上的黏着。一个梯度构象变化发生在胞外已活化的整合蛋白的一个区域上。现在整合蛋白可以与内皮细胞表面的I-cam相作用。这种强烈的相互作用使滚动着的白细胞在察觉到信息时停了下来。附加的信息引起细胞骨架的大规模改组，使得白细胞的一个边缘扩散而形成了刀锋状。白细胞的锋状边缘将自己插入到内皮细胞的孔隙中，白细胞便穿越了血管壁而进入发炎的组织。滚动、激活、附着和穿过内皮细胞是一个过程的四个步骤，这个过程被称作白细胞的应激反应。
Velocity [vi'l?siti]n. 速度, 速率, 迅速, 周转率
Leukocyte ['lju:k?sait] n.[解]白细胞, 白血球
endothelial cell 内皮细胞
Glycoprotein [?glaik?u'pr?uti:n]n. [化]糖蛋白类, 醣蛋白
Microvilli [?maikr?u'vilai] microvillus的复数
Microvillus [?maikr?u'vil?s]n. [生](细胞表面的)微绒毛,微小突起物,指状突
Sphingolipid [?sfi?g?u`lipid,-`lai-] n. [生化](神经)鞘脂类
Phosphotidylcholine [?f?sf?'taidl'k?uli:n]] n. [生化]
Cholesterol [k?'lest?r?ul, -r?l] n. 胆固醇
Hydrocarbon ['haidr?u'ka:b?n] n. 烃, 碳氢化合物
Chemokinesis [?kem?ukai'ni:sis] (生物的)化学运动性
Heparan ['hep?r?n] a.乙酰(型)肝素 b.类肝素
Proteoglycan [pr?uti?'glaikæn] n. [生化]蛋白聚糖,蛋白多糖
Cascade [kæs'keid] n.小瀑布, 喷流 vi.成瀑布落下 n.层叠
Spectrin [`spektrin] n. [生化]血影蛋白,幽灵蛋白
Tetramer ['tetr?m?] n. [化]四聚物
Hexagonal [hek`sæg?n?l] adj. 六角形的, 六边形的
actin filament 肌(动蛋白)丝
Cytosol ['sait?us?l] n. [生]细胞溶质,胞液
Polymerization [?p?lim?rai'zei??n] n. 聚合
Microtubule [? maikr?u'tju:bju:l] n. [生]微管
Centriole ['sentri?ul] n. [生]细胞中心粒,中心体
Ribosome ['raib?s?um] n. [生化]核糖体
Mitochondria [?mait?'k?ndri?] [生]线粒体
Endoplasmic reticulum 内质网
Reticulum [ri'tikjul?m] n. 网状组织
Glycosylation [?glaik?si`lei??n] n. [生化]糖基化
Lumen ['lju:min] n. 流明（光通量单位）, [解]内腔
Extravasation [eks?træv?'sei??n] n. 溢出, 溢出物, [地]熔岩外喷
英文解说供参考：
- First shot: circulation. Red blood cells and platelets move extraordinarily fast through the bloodstream while many white blood cells roll along the walls of your blood vessels. This allows the WBCs to respond to signals that it should break through the vessel wall and help out (if it were unattached it wouldn't be able to land in time to be anywhere near where it was needed)
- Next we zoom in on the white blood cell's rolling process. We see that this happens because proteins sticking out from the WBC stick to proteins sticking out from the cells lining the blood vessel (these proteins are called CAMs, or cellular adhesion molecules. I forget exactly what kind of CAM mediates this kind of cell-cell adhesion, but there are subtypes). We also see the extracellular matrix in this shot -- that's the fibrous stuff covering the outside of the cell, giving it rigidity (it's made up of proteins like collagen... inside your body, if it breaks it lets out a signal to nearby cells to grow and fill in the break, if you're cut for example). One thing to note about CAM adhesion is that two proteins don't generally stick together, they have to be specifically tailed for that function.
- Next we zoom in further on the surface of the cell, beyond the extra cellular matrix. We sea the sea of lipids (blue and green round things) that make up the boundary of the cell, and we see a raft floating through them. This is a "lipid raft", and it has more cholesterol in it than the rest of the cellular membrane. These rafts are special places for certain proteins and lipids to aggregate (i.e., some proteins designed to accept signals from the environment will aggregate in these -- an example of a signal is a hormone like insulin, which when it attaches to a protein designed to catch it will cause a cell to change metabolism, for example).
- Next we see two proteins making contact (the red one hanging down and the purple one sticking up). I don't know what these proteins are, but my guess is that the vessel cell is signaling to the WBC that the WBC should invade the tissue (i.e., there's damage and the inflammatory process sends signals that eventually get to WBCs, which then come to help).
- A pretty shot zoomed out of a raft floating along the cell surface
- I don't know what the trinagular structres are, which is frustrating. Maybe it's actin covering the interior wall of the cell? Actin is a cytoskeletal protein (i.e., it makes up a rigid structural and transport network) that covers the interior side of the cellular membrane. It's a meeting point between things on the inside of the cell and the cellular membrane (which is useful, for example, if a signal is received on the cell surface and needs to trickle into intracellular components).
- Next is the purple and green lattice. I think this is actin with cross-linking proteins. Actin fibers (actin is made up of protein subunits that form those long, twisty fibers) don't just randomly stack, they're also connected to each other by proteins to make the dense structure you see here.
- Next we see actin polymerization (the purple fibrils self-assembling). This is a spontaneous process that happens when the concentrations of actin are high enough (and it looks really cool here). The cell tightly regulates the concentration of actin so as to make the right amount of these fibers.
- Next we see the small green protein stick to actin, breaking it up. Our cells will activate these proteins if they want to break down that huge actin lattice we saw earlier very quickly (i.e., when the cell is moving). An interesting sidenote is how well the proteins fit together. This isn't artistic license, these proteins' 3D structures are modeled after real life.
- Next the huge green tube -- this is a microtubule assembling. Like actin, this is a spontaneous process dictated by concentration. Microtubules are made up of alternating alpha and beta subunits. Then we see the microtubule dissassembling. Notice how it frays at the end and then completely falls apart...I think that's a realistic rendering.
- Next is what I think is the coolest part, the little walker along the microtubule. That's a kinesin, a protein that literally walks along microtubules to carry cargo around the cell. This is how things end up at their destinations without having to just float around until they hit the right thing. Microtubules are organized to radiated from a microtubule organizing center out to the cell surface. Here a kinesin is walking in a specific direction (I assume toward the cell surface) because its cargo, a huge vesicle, needs to get there. Vesicles are little lipid-bound blobs that carry stuff around -- so this all is the FedEx of the cell. Kinesins are fascinating proteins -- they don't walk without energy input, since the walking requires work. ATP is involved.
- Then we zoom out and see the MTOC (microtubule organizing center) in the background (the sphere with two orthogonal cylinders in front). Microtubules emanate from there. MTOCs are pretty interesting things because they have to multiply and divide with the rest of the cell, and we don't know exactly how that works yet.
- Now we've changed venues...we see a round surface with little holes. That round surface is the nucleus, where DNA lives. Those holes are nuclear pores, which is how things get in and out of the nucleus. DNA is transcribed into RNA in the nucleus, and that RNA is then transported out of the cell where it is translated into proteins by ribosomes. In higher order organisms the RNA makes a circle as you see here. If you look closely you can see the small subunit of the ribosome attach to the RNA and scan along until it finds the start sequence on the RNA, where the large subunit then attaches.
- Then we zoom in on the ribosome reading the RNA and spitting out the growing protein. Pretty cool shot.
- Next is the blue and red proteins floating over to the huge cylindrical blob. I don't know if that's a proteasome or a chaperone...I think it's a chaperone. Anyway, the role of a chaperone is to take in a newly synthesized protein and fold it properly. There's lots of research going on into how exactly this happens right now (i.e., Fold@Home).
- The next shot is translation again (see the yellow-green ribosome and the RNA stuck in it). This time translation is happening into the Endoplasmic Reticulum, however, because the protein it's making needs to be secreted out of the cell. This is where that process starts (proteins meant for secretion aren't just made in the cytosol and then magically end up on the outside of the cell. They're spit into this special compartment where its exit from the cell is ordered).
- Next is some vesicle formation, I assume off of the ER and toward the golgi apparatus, which is the next stop in the secretory pathway for proteins destined for the outside of the cell. We see the kinesin in the foreground again.
- Next we see the vesicle arriving at the golgi apparatus, the large layer of blobby pancakes. Vesicles from the ER arrive at one end and progress through the layers, where they're either targeted for other parts of the cell, or if not will exit via a vesicle to the cell membrane.
- Now we see a huge cavity opening up and things flying out of the cell. This is what happens when a vesicle makes it to the cell membrane -- it fuses, releasing its contents outside. Proteins that were in the vesicle membrane are now part of the cellular membrane. The orientation of these membrane-attached proteins is controlled so that they face the right way.
- Then we see raft formation, I think, around a set of proteins.
- Then we zoom out and see the result of the signal to the WBC -- it invades through the blood vessel wall to the surrounding tissue. I don't know anything about the immune system, though, so my details on the macro aspect are sketchy and possibly incorrect.
以上是在网上搜集到的内容，并经daniellad编辑整理。值得生物专业人士学习。
中文视频：点这，251.50MB，用迅雷下载，不过速度比较慢，请大家耐心下载。
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