高尔基体近中心体堆叠重组
中文名称
通路描述
在细胞分裂期间，高尔基体近中心体堆叠发生广泛的碎片化和重组。哺乳动物细胞中的高尔基体由连接成管状的高尔基囊泡堆叠而成的带状结构组成，位于核周区域，靠近中心体。细胞分裂期间高尔基体的重组允许两个子细胞继承该细胞器，并可能在纺锤体组织中发挥额外作用。高尔基体结构的第一次变化可能始于 G2 期，涉及高尔基带状结构解离为独立堆叠，这是哺乳动物细胞进入有丝分裂所必需的。这种高尔基带状结构的初始解离依赖于 GRASP 蛋白和 CTBP1（BAR）蛋白，后者诱导连接堆叠的管状膜裂解，但确切机制尚不清楚。MEK1/2 的激活也有助于 G2 期高尔基带状结构的解离。从有丝分裂前期到中期，高尔基体囊泡发生广泛的碎片化，这是高尔基体解离和运输停止的结果。CDK1、PLK1 和 MEK1 至少三种有丝分裂激酶调节这些变化。CDK1 与 Cyclin B 复合物磷酸化 GOLGA2（GM130）和 GORASP1（GRASP65），它们是顺面高尔基体膜复合物的成分。GOLGA2 的磷酸化阻止 USO1（p115）蛋白与 ER 到高尔基体运输囊泡和顺面高尔基体的结合，从而抑制这些囊泡与顺面高尔基囊泡的融合，停止 ER 到高尔基体的运输。GORASP1 的磷酸化由 CDK1 介导，并进一步由 PLK1 磷酸化。CDK1 和 PLK1 对 GORASP1 的磷酸化干扰了 GORASP1 转寡聚体的形成，从而阻碍高尔基体囊泡的堆叠。在中间高尔基体中，GORASP2（GRASP55），一种与 BLFZ1（高尔基蛋白-45）和 RAB2A GTPase 形成复合物并参与囊泡堆叠和高尔基体运输的蛋白，也在有丝分裂期间被磷酸化。MEK1/2 激活的 MAPK1（ERK2）和/或 MAPK3-3（人类 ERK1b，大鼠 Erk1c）对 GORASP2 的磷酸化也有贡献，有助于 G2 期高尔基体解离和有丝分裂前期高尔基体囊泡的碎片化。
英文描述
Heme signaling Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups upon oxidation. Blood plasma contains proteins that scavenge heme. It is estimated that about 2â8% of the heme released in plasma becomes âbioavailableâ, being internalized by bystander cells. If the heme degradation capacity of a cell, represented by heme oxidase 1 and 2, cannot be ramped up sufficiently then heme signaling and reactivity puts cells under stress. Platelets are activated by heme, and macrophages switch to the inflammatory type (Donegan et al, 2019; Gouveia et al, 2019).
Free (labile) heme accumulates in the blood stream in great amounts under pathological conditions like viral infections and malaria, but also ARDS amd COPD. The locally affected cells' primary reaction is to upregulate heme oxidase 1 (HMOX1) expression. HMOX1 induction in these cells not only removes heme from circulation but also triggers a functional switch toward the anti-inflammatory phenotype (Vijayan et al, 2018). However, heme scavenging and degradation systems may get overwhelmed by the sheer amount of heme present.
Heme promotes platelet activation, complement activation, vasculitis, and thrombosis (Bourne et al, 2020; Merle et al, 2018). Heme was recognized to act as a danger signal, damage-associated molecular pattern (DAMP), or alarmin (Soares and Bozza, 2016) and was shown to activate Toll-like receptor 4 (TLR4) signaling (Figueiredo et al, 2007; Janciauskiene et al, 2020). It also has a role as corepressor in the circadian clock system (Ko and Takahashi, 2006). BACH1 is regulated by heme in a cell, thus placing heme as a signaling molecule in gene expression in higher eukaryotes. The regulation of BACH1 by heme may be important for the stress response in general (Suzuki et al, 2004).
Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups uponoxidation. Due to the reactive nature of free heme, the blood plasma contains proteins that scavenge heme. It is estimated that about 2â8% of the heme released in plasma becomes âbioavailableâ, being internalized by bystander cells. Failure of nearby cells to sufficientlymetabolize free heme can incite platelet activation, macrophage differentiation, and oxidative stress (Donegan et al, 2019; Gouveia et al, 2019).
Free (labile) heme accumulates in the blood stream in great amounts under pathological conditions like viral infections and malaria, but also ARDS amd COPD. The locally affected cells' primary reaction is to upregulate heme oxidase 1 (HMOX1) expression. HMOX1 induction in these cells not only removes heme from circulation but also triggers a functional switch toward the anti-inflammatory phenotype (Vijayan et al, 2018). However, heme scavenging and degradation systems may get overwhelmed by the sheer amount of heme present.
Heme promotes platelet activation, complement activation, vasculitis, and thrombosis (Bourne et al, 2020; Merle et al, 2018). Heme was recognized to act as a danger signal, damage-associated molecular pattern (DAMP), or alarmin (Soares and Bozza, 2016) and was shown to activate Toll-like receptor 4 (TLR4) signaling (Figueiredo et al, 2007; Janciauskiene et al, 2020). It also has a role as corepressor in the circadian clock system (Ko and Takahashi, 2006). BACH1 is regulated by heme in a cell, thus placing heme as a signaling molecule in gene expression in higher eukaryotes. The regulation of BACH1 by heme may be important for the stress response in general (Suzuki et al, 2004).
Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups uponoxidation. Due to the reactive nature of free heme, the blood plasma contains proteins that scavenge heme. It is estimated that about 2â8% of the heme released in plasma becomes âbioavailableâ, being internalized by bystander cells. Failure of nearby cells to sufficientlymetabolize free heme can incite platelet activation, macrophage differentiation, and oxidative stress (Donegan et al, 2019; Gouveia et al, 2019).
所含基因
46 个基因