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哈佛大學分子與細胞系的學生和Xvivo動畫製作公司，合作的影片-The Inner Life of the Cell
內容是白血球如何感覺周圍環境，並對外部刺激迅速做出回應，動畫做得很細膩
(上面這部動畫是沒有說明的部分，如要聽說明，請點選下面連結)
影片連結
英文聽打: guyspy, jeff31303; 中文翻譯: guyspy, jeff31303; 校對: 蘇懿生 老師
While red blood cells are carried away at high velocity by a strong blood flow, leukocytes roll slowly on endothelial cells. P-selectins on endpthelial cells interact with PSGL-1, a glycoprotein on leukocyte microvilli. Leukocytes, pushed by the blood flow, adhere and roll on endothelial cells, because existing interaction are broken, while new ones are formed. These interactions are possible because the extended extra cellular domains of both proteins emerge from the extra cellar matrix, which cover the surface of both cell types.
The outer leaflet of the lipid bilayers is enriched in sphingolipids and phosphatidylcholine. Sphingolipid-rich raft raise above the rest of the leaflet, recruit specific membrane proteins. Raft rigidity is cause by the tight packing of cholesterol molecules against the straight sphingolipids hydrocarbon chains. Outside the raft, kinks and unsaturated hydrocarbon chain, and lower cholestrol concentration, result in increased fluidity.
At sites of inflammation, secreted chemokine bound to heparin sulfate proteoglycan on endothelial cells are presented to leukocyte seven-transmembrane receptors. The binding stimulates leukocytes, and triggers an intercellular cascade of signalling reactions.
The inner leaflet of the bilayer has a very different composition than that of the outer leaflet. While some proteins traverse the membrane, others are ether anchored to the inner leaflet by covalently attached fatty acid chains, or are recruited through non-covalent interaction with membrane proteins. The membrane-bond protein complexes are critical for the transmission of signals across the plasma membrane.
Beneath the lipid bilayer, spectrin tetramers, arranged into a hexagonal network, are anchored by membrane protein. This network forms a membrane skeleton that contributes to membrane stability and membrane protein distribution. The cytoskeleton is comprised of networks of filamentous proteins that are responsible for the special organization of cytosolic components. Inside microvilli, actin filaments form tight parallel bundles which are stabalized by cross-linking proteins. While deeper in the cytosol, the actin network adopts a gel-like structure, stabalized by a variety of actin binding proteins. Filaments, capped at their minus end by a protein complex, grow away from the plasma membrane by the addition of actin monomers to their plus ends. The actin network is a very dynamic structure, with continuous directional polymerization and disassembly. Severing proteins induces kinks in the filaments, and leads to the formation of short fragments that rapidly depolymerize or give rise to new filaments. The cytoskeleton includes a network of microtubules created by the lateral association of protofilaments formed by the polymerization of tubulin dimers.
While the plus end of some microtubules extends toward the plasma membrane, proteins stabilize the curved conformation of the protofilaments from other microtubules, causing their rapid plus end depolymerization. Microtubules provide tracks along which membrane-bound 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 bound organells 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 microtubule originates from the centrosome, a discrete fibrous structure containing two orthogonal centrioles and located near the cell nucleus. Pores of 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 are reside in the cytosol, others are associated with specialized cytosolic proteins and been imported into mitochondria or other organelles. The synthesis of cell-secreted and integral membrane proteins is initiated by free ribosomes, which than dock to protein translocator at the surface of the endoplasmic reticulum.
Nascent proteins pass through an aqueous pore in the translocator. Cell secreted proteins accumulated in the lumen of the endoplasmic reticulum, while integral membrane proteins become embedded in the endoplasmic reticulum membrane. Proteins are transported from the endoplasmic reticulum to the Golgi apparatus by vesicles traveling along the microtubules. Protein glycosylation, initiated in the endoplasmic reticulum, is completed inside the lumen of the Golgi apparatus. Fully glycosylated proteins are transported from the Golgi apparatus to the plasma membrane. While the vesicle fuses with the plasma membrane, proteins contained in the vesicle lumen are secreted, and proteins embedded in the vesicle membrane diffuse in the cell membrane.
At sites of inflammation, chemokine secreted by endothelial cells binds to the extracellular domains of G-protein coupled receptors. This binding causes a conformational change in the cytosolic portion of the receptor, and the consequent activation of the subunit of the G-protein. The activation of the G-protein subunit triggers a cascade of protein activation, which in turn lead to the activation and clustering of integrin inside lipid rafts. A dramatic conformational change occurs in the extracellular domain of the activated integrins. This now allowed for their interaction with I-Cam proteins display at the surface of the endothelial cells. These strong interactions immobilized the rolling leukocyte at the site of inflammation. Additional signaling event cause a profound reorganization of the cytoskeleton, result in the spreading of one edge of the leukocyte.
The leading edge of the leukocyte inserts itself between the endothelial cells, and the leukocyte migrates through the blood vessel wall into the inflammed tissue. Rolling, activation, adhesion, and trans-endothelial migration are the four steps of the process called leukocyte extravasation.
當紅血球在血管裡被滾滾血流快速運送時，白血球則是沿著血管內皮細胞緩慢地滾動著。 這是由於白血球的微絨毛上有PSGL-1醣蛋白，會和內皮細胞表面的P-seletins蛋白互相黏結。當白血球被血流向前推進時，舊有的黏結會斷裂，並生成新的黏結，白血球因而貼附著內皮細胞向前滾動。
這些反應之所以能進行，是由於這兩種蛋白都從胞外基質中突出而外露，使彼此能互相接觸。脂質雙層膜的外層富含神經脂質(或稱鞘脂質, sphingolipids)和卵磷脂(phosphatidylcholine)，神經脂質的分子長度高出於其餘的外層膜磷脂，因此聚集而形成「脂質小舟」，並會攜帶特定的膜蛋白。「小舟」內排列緻密的膽固醇分子緊貼著神經脂質的碳氫長鏈，可以維持小舟的穩定。在「小舟」之外的細胞膜，是由彎折、不飽和的碳氫鏈，和較低濃度的膽固醇所組成，因此流動性較高。
在發炎感染處分泌出來的趨化因子(chemokine)，會與紅血球細胞膜上的HSPG蛋白多醣(heparin sulfate proteoglycan, HSPG)連接；此趨化因子接著便被呈現給白血球表面的七次跨膜受體，這樣的結合會刺激白血球，並啟動其細胞內一連串的梯瀑傳訊反應。
脂雙層膜的內層組成和外層有明顯不同，有些蛋白分子直接穿膜而過，有些則是利用共價鍵固定在內層膜的脂肪酸鏈上，或是透過非共價鍵結與膜蛋白連接。這些與細胞膜相連的蛋白質複合體，是跨越細胞膜傳遞訊息的關鍵。在脂雙層膜的下方，六角形網狀結構的血影蛋白(spectrin)四聯體固定在膜蛋白上，這個網狀結構形成一套細胞膜的骨架，可強化細胞膜的穩定性，並影響膜蛋白的分布。
細胞骨架是由一群絲狀蛋白所組成的網狀結構，負責胞內各種特定架構的形成。在微絨毛內部，微絲藉由許多交叉連結的蛋白質，形成緊密而平行的纖維束。然而在更深層的細胞液中，微絲骨架藉由各種微絲附屬蛋白，形成類似膠狀的結構。微絲的負端被蛋白質複合體所覆蓋，肌凝蛋白單體則是從纖維的正端加入，造成纖維自細胞膜向內延長。微絲骨架是一種非常動態的結構，不斷地進行著具有方向性的聚合與拆解作用。剪接蛋白能將微絲扭斷，而形成短片段，此片段會快速地拆解，或是產生新的微絲纖維。細胞骨架也包含微管骨架。微管骨架是由微管蛋白(tubulin)聚合成的許多原絲(protofilament)，進行側向聯結所形成的網狀架構。
有些微管的正端會向細胞膜的方向延伸，同時另一些微管的原絲則受其他蛋白的影響而彎曲，進而造成其從正端的快速拆解。微管同時也作為囊泡往來細胞膜的移動軌道，這些運貨囊泡特定方向性的移動，源自於一群將囊泡和微管連結在一起的動力蛋白分子。其他膜狀胞器，例如粒線體，會和細胞骨架輕微地連結。粒線體會不斷的改變形狀，而它們的排列方向有一部份就是由和微管的互動所決定的。
所有的微管都源自於中心體。中心體位於細胞核附近，是一個獨立的纖維狀結構，其中包含有兩個互相垂直的中心粒。核膜上的核孔使得mRNA和蛋白質分子能進入細胞液中，在此，游離的核糖體將mRNA分子轉譯成蛋白質。有些蛋白質會留存在細胞液中，有些則會和細胞液中特定的蛋白結合，而被運送到粒線體或是其他胞器。細胞外泌的蛋白質以及膜蛋白的合成，始於游離核糖體的轉譯，這些核糖體接著便會連接到內質網膜上的轉運蛋白，新合成中的蛋白質分子隨後穿過轉運蛋白中間的水溶性孔道， 細胞外泌的蛋白質分子聚積在內質網的腔室裡，而膜蛋白則會嵌入內質網膜中。這些蛋白質分子接著匯入囊泡中，沿著微管，由內質網送往高基氏體。
蛋白質分子的醣化修飾，起始於內質網，最後在高基氏體的腔室內完成。完成醣化修飾的蛋白質分子，隨後從高基氏體被運往細胞膜。當囊泡和細胞膜融合的時候，囊泡內的蛋白分子於是分泌到細胞外，而鑲嵌在囊泡膜上的蛋白分子便在細胞膜上擴散，成為膜蛋白。
在組織發炎處，內皮細胞分泌的趨化因子，會與白血球表面的G-蛋白相連受體結合，此結合於是造成受體的胞內區域發生構形改變，並活化了G蛋白的一個次單元，此G蛋白次單元的活化，啟動了連鎖的蛋白質活化反應，進而造成細胞聯結蛋白(integrin)於脂質小舟裡聚集並活化。 細胞聯結蛋白活化後，它的胞外區域發生劇烈的構形改變，這樣的構形改變，使得它可以和血管內皮細胞上的細胞聯繫蛋白I-Cam相聯接。這些作用力較為堅固，使得白血球的滾動於發炎處暫停下來。
之後，其他的訊息進一步引發白血球的細胞骨架發生大規模的重整，使得白血球的邊緣攤平， 隨後白血球的細胞前緣便插入內皮細胞間的縫隙，於是白血球藉此方式，得以穿過血管壁進入發炎的組織。滾動，活化，黏附，以及跨內皮細胞的遷徙，是白血球外滲作用的四個主要步驟。
內容是白血球如何感覺周圍環境，並對外部刺激迅速做出回應，動畫做得很細膩
(上面這部動畫是沒有說明的部分，如要聽說明，請點選下面連結)
影片連結
英文聽打: guyspy, jeff31303; 中文翻譯: guyspy, jeff31303; 校對: 蘇懿生 老師
While red blood cells are carried away at high velocity by a strong blood flow, leukocytes roll slowly on endothelial cells. P-selectins on endpthelial cells interact with PSGL-1, a glycoprotein on leukocyte microvilli. Leukocytes, pushed by the blood flow, adhere and roll on endothelial cells, because existing interaction are broken, while new ones are formed. These interactions are possible because the extended extra cellular domains of both proteins emerge from the extra cellar matrix, which cover the surface of both cell types.
The outer leaflet of the lipid bilayers is enriched in sphingolipids and phosphatidylcholine. Sphingolipid-rich raft raise above the rest of the leaflet, recruit specific membrane proteins. Raft rigidity is cause by the tight packing of cholesterol molecules against the straight sphingolipids hydrocarbon chains. Outside the raft, kinks and unsaturated hydrocarbon chain, and lower cholestrol concentration, result in increased fluidity.
At sites of inflammation, secreted chemokine bound to heparin sulfate proteoglycan on endothelial cells are presented to leukocyte seven-transmembrane receptors. The binding stimulates leukocytes, and triggers an intercellular cascade of signalling reactions.
The inner leaflet of the bilayer has a very different composition than that of the outer leaflet. While some proteins traverse the membrane, others are ether anchored to the inner leaflet by covalently attached fatty acid chains, or are recruited through non-covalent interaction with membrane proteins. The membrane-bond protein complexes are critical for the transmission of signals across the plasma membrane.
Beneath the lipid bilayer, spectrin tetramers, arranged into a hexagonal network, are anchored by membrane protein. This network forms a membrane skeleton that contributes to membrane stability and membrane protein distribution. The cytoskeleton is comprised of networks of filamentous proteins that are responsible for the special organization of cytosolic components. Inside microvilli, actin filaments form tight parallel bundles which are stabalized by cross-linking proteins. While deeper in the cytosol, the actin network adopts a gel-like structure, stabalized by a variety of actin binding proteins. Filaments, capped at their minus end by a protein complex, grow away from the plasma membrane by the addition of actin monomers to their plus ends. The actin network is a very dynamic structure, with continuous directional polymerization and disassembly. Severing proteins induces kinks in the filaments, and leads to the formation of short fragments that rapidly depolymerize or give rise to new filaments. The cytoskeleton includes a network of microtubules created by the lateral association of protofilaments formed by the polymerization of tubulin dimers.
While the plus end of some microtubules extends toward the plasma membrane, proteins stabilize the curved conformation of the protofilaments from other microtubules, causing their rapid plus end depolymerization. Microtubules provide tracks along which membrane-bound 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 bound organells 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 microtubule originates from the centrosome, a discrete fibrous structure containing two orthogonal centrioles and located near the cell nucleus. Pores of 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 are reside in the cytosol, others are associated with specialized cytosolic proteins and been imported into mitochondria or other organelles. The synthesis of cell-secreted and integral membrane proteins is initiated by free ribosomes, which than dock to protein translocator at the surface of the endoplasmic reticulum.
Nascent proteins pass through an aqueous pore in the translocator. Cell secreted proteins accumulated in the lumen of the endoplasmic reticulum, while integral membrane proteins become embedded in the endoplasmic reticulum membrane. Proteins are transported from the endoplasmic reticulum to the Golgi apparatus by vesicles traveling along the microtubules. Protein glycosylation, initiated in the endoplasmic reticulum, is completed inside the lumen of the Golgi apparatus. Fully glycosylated proteins are transported from the Golgi apparatus to the plasma membrane. While the vesicle fuses with the plasma membrane, proteins contained in the vesicle lumen are secreted, and proteins embedded in the vesicle membrane diffuse in the cell membrane.
At sites of inflammation, chemokine secreted by endothelial cells binds to the extracellular domains of G-protein coupled receptors. This binding causes a conformational change in the cytosolic portion of the receptor, and the consequent activation of the subunit of the G-protein. The activation of the G-protein subunit triggers a cascade of protein activation, which in turn lead to the activation and clustering of integrin inside lipid rafts. A dramatic conformational change occurs in the extracellular domain of the activated integrins. This now allowed for their interaction with I-Cam proteins display at the surface of the endothelial cells. These strong interactions immobilized the rolling leukocyte at the site of inflammation. Additional signaling event cause a profound reorganization of the cytoskeleton, result in the spreading of one edge of the leukocyte.
The leading edge of the leukocyte inserts itself between the endothelial cells, and the leukocyte migrates through the blood vessel wall into the inflammed tissue. Rolling, activation, adhesion, and trans-endothelial migration are the four steps of the process called leukocyte extravasation.
當紅血球在血管裡被滾滾血流快速運送時，白血球則是沿著血管內皮細胞緩慢地滾動著。 這是由於白血球的微絨毛上有PSGL-1醣蛋白，會和內皮細胞表面的P-seletins蛋白互相黏結。當白血球被血流向前推進時，舊有的黏結會斷裂，並生成新的黏結，白血球因而貼附著內皮細胞向前滾動。
這些反應之所以能進行，是由於這兩種蛋白都從胞外基質中突出而外露，使彼此能互相接觸。脂質雙層膜的外層富含神經脂質(或稱鞘脂質, sphingolipids)和卵磷脂(phosphatidylcholine)，神經脂質的分子長度高出於其餘的外層膜磷脂，因此聚集而形成「脂質小舟」，並會攜帶特定的膜蛋白。「小舟」內排列緻密的膽固醇分子緊貼著神經脂質的碳氫長鏈，可以維持小舟的穩定。在「小舟」之外的細胞膜，是由彎折、不飽和的碳氫鏈，和較低濃度的膽固醇所組成，因此流動性較高。
在發炎感染處分泌出來的趨化因子(chemokine)，會與紅血球細胞膜上的HSPG蛋白多醣(heparin sulfate proteoglycan, HSPG)連接；此趨化因子接著便被呈現給白血球表面的七次跨膜受體，這樣的結合會刺激白血球，並啟動其細胞內一連串的梯瀑傳訊反應。
脂雙層膜的內層組成和外層有明顯不同，有些蛋白分子直接穿膜而過，有些則是利用共價鍵固定在內層膜的脂肪酸鏈上，或是透過非共價鍵結與膜蛋白連接。這些與細胞膜相連的蛋白質複合體，是跨越細胞膜傳遞訊息的關鍵。在脂雙層膜的下方，六角形網狀結構的血影蛋白(spectrin)四聯體固定在膜蛋白上，這個網狀結構形成一套細胞膜的骨架，可強化細胞膜的穩定性，並影響膜蛋白的分布。
細胞骨架是由一群絲狀蛋白所組成的網狀結構，負責胞內各種特定架構的形成。在微絨毛內部，微絲藉由許多交叉連結的蛋白質，形成緊密而平行的纖維束。然而在更深層的細胞液中，微絲骨架藉由各種微絲附屬蛋白，形成類似膠狀的結構。微絲的負端被蛋白質複合體所覆蓋，肌凝蛋白單體則是從纖維的正端加入，造成纖維自細胞膜向內延長。微絲骨架是一種非常動態的結構，不斷地進行著具有方向性的聚合與拆解作用。剪接蛋白能將微絲扭斷，而形成短片段，此片段會快速地拆解，或是產生新的微絲纖維。細胞骨架也包含微管骨架。微管骨架是由微管蛋白(tubulin)聚合成的許多原絲(protofilament)，進行側向聯結所形成的網狀架構。
有些微管的正端會向細胞膜的方向延伸，同時另一些微管的原絲則受其他蛋白的影響而彎曲，進而造成其從正端的快速拆解。微管同時也作為囊泡往來細胞膜的移動軌道，這些運貨囊泡特定方向性的移動，源自於一群將囊泡和微管連結在一起的動力蛋白分子。其他膜狀胞器，例如粒線體，會和細胞骨架輕微地連結。粒線體會不斷的改變形狀，而它們的排列方向有一部份就是由和微管的互動所決定的。
所有的微管都源自於中心體。中心體位於細胞核附近，是一個獨立的纖維狀結構，其中包含有兩個互相垂直的中心粒。核膜上的核孔使得mRNA和蛋白質分子能進入細胞液中，在此，游離的核糖體將mRNA分子轉譯成蛋白質。有些蛋白質會留存在細胞液中，有些則會和細胞液中特定的蛋白結合，而被運送到粒線體或是其他胞器。細胞外泌的蛋白質以及膜蛋白的合成，始於游離核糖體的轉譯，這些核糖體接著便會連接到內質網膜上的轉運蛋白，新合成中的蛋白質分子隨後穿過轉運蛋白中間的水溶性孔道， 細胞外泌的蛋白質分子聚積在內質網的腔室裡，而膜蛋白則會嵌入內質網膜中。這些蛋白質分子接著匯入囊泡中，沿著微管，由內質網送往高基氏體。
蛋白質分子的醣化修飾，起始於內質網，最後在高基氏體的腔室內完成。完成醣化修飾的蛋白質分子，隨後從高基氏體被運往細胞膜。當囊泡和細胞膜融合的時候，囊泡內的蛋白分子於是分泌到細胞外，而鑲嵌在囊泡膜上的蛋白分子便在細胞膜上擴散，成為膜蛋白。
在組織發炎處，內皮細胞分泌的趨化因子，會與白血球表面的G-蛋白相連受體結合，此結合於是造成受體的胞內區域發生構形改變，並活化了G蛋白的一個次單元，此G蛋白次單元的活化，啟動了連鎖的蛋白質活化反應，進而造成細胞聯結蛋白(integrin)於脂質小舟裡聚集並活化。 細胞聯結蛋白活化後，它的胞外區域發生劇烈的構形改變，這樣的構形改變，使得它可以和血管內皮細胞上的細胞聯繫蛋白I-Cam相聯接。這些作用力較為堅固，使得白血球的滾動於發炎處暫停下來。
之後，其他的訊息進一步引發白血球的細胞骨架發生大規模的重整，使得白血球的邊緣攤平， 隨後白血球的細胞前緣便插入內皮細胞間的縫隙，於是白血球藉此方式，得以穿過血管壁進入發炎的組織。滾動，活化，黏附，以及跨內皮細胞的遷徙，是白血球外滲作用的四個主要步驟。
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