Caveolin isoform switching as a molecular, structural, and metabolic regulator of microglia.
Caveolin isoform switching as a molecular, structural, and metabolic regulator of microglia.
复制标题
DOI：
10.1016/j.mcn.2013.07.002
复制
发表时间：
2013-09
影响因子：
3.5
通讯作者：
Patel, Hemal H.
中科院分区：
文献类型：
--
作者：
Niesman, Ingrid R.;Zemke, Nathan;Fridolfsson, Heidi N.;Haushalter, Kristofer J.;Levy, Karen;Grove, Anna;Schnoor, Rosalie;Finley, J. Cameron;Patel, Piyush M.;Roth, David M.;Head, Brian P.;Patel, Hemal H.
小胶质细胞是作为中枢神经系统（CNS）监护者的分支细胞，能够增殖、迁移和产生炎性细胞因子。在非病理状态下，这些细胞表现出分枝形态，具有与神经元和星形胶质细胞混合的突起。在病理条件下，它们获得圆形变形虫形态和增殖和迁移能力。这种形态学变化需要细胞骨架重排。微管和肌动蛋白聚合状态的分子控制点仍在研究中。Caveolin（Cav），膜/脂筏蛋白，在炎性细胞中表达，但Caveolin同种型在小胶质细胞生理学中的作用是有争议的。我们建议小窝蛋白提供了一个必要的控制点，在细胞骨架动力学的调节，从而研究了小窝蛋白在小胶质细胞生物学中的作用。我们检测了Cav-1和Cav-3的mRNA和蛋白。Cav-1蛋白明显减少，并定位于质膜（PM）和细胞质囊泡（CV）的小胶质细胞的非活性状态，而活跃（变形虫形）的小胶质细胞表现出增加Cav-1的表达。相反，Cav-3在非活性状态下高度表达，并定位于细胞突起和核周区域，并在活性阿米巴样小胶质细胞中检测到。在活性或非活性状态下的细胞骨架的药理学操作改变了小窝蛋白的表达。此外，增加Cav-1表达也增加线粒体呼吸，这表明可能在细胞代谢中的调节作用，以促进形态学变化。目前的研究结果强烈表明，小胶质细胞的形态和活性的调节部分是由于小窝蛋白亚型，在中枢神经系统损伤或疾病提供了有前途的新的治疗靶点。
Microglia are ramified cells that serve as central nervous system (CNS) guardians, capable of proliferation, migration, and generation of inflammatory cytokines. In non-pathological states, these cells exhibit ramified morphology with processes intermingling with neurons and astrocytes. Under pathological conditions, they acquire a rounded amoeboid morphology and proliferative and migratory capabilities. Such morphological changes require cytoskeleton rearrangements. The molecular control points for polymerization states of microtubules and actin are still under investigation. Caveolins (Cav), membrane/lipid raft proteins, are expressed in inflammatory cells, yet the role of Caveolin isoforms in microglia physiology is debatable. We propose caveolins provide a necessary control point in the regulation of cytoskeletal dynamics, and thus investigated a role for caveolins in microglia biology. We detected mRNA and protein for both Cav-1 and Cav-3. Cav-1 protein was significantly less and localized to plasmalemma (PM) and cytoplasmic vesicles (CV) in the microglial inactive state, while the active (amoeboid-shaped) microglia exhibited increased Cav-1 expression. In contrast, Cav-3 was highly expressed in the inactive state and localized with cellular processes and perinuclear regions and was detected in active amoeboid microglia. Pharmacological manipulation of the cytoskeleton in the active or non-active state altered caveolin expression. Additionally, increased Cav-1 expression also increased mitochondrial respiration, suggesting possible regulatory roles in cell metabolism necessary to facilitate the morphological changes. The present findings strongly suggest that regulation of microglial morphology and activity are in part due to caveolin isoforms, providing promising novel therapeutic targets in CNS injury or disease.
登录
查看更多内容
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
6.7
作者：
Larson, Kelley C.;Draper, Michael P.;Dabrowski, Michal
通讯作者：
Dabrowski, Michal
影响因子：
6
作者：
Mirza, Muhammad K.;Yuan, Jun;Zhao, You-Yang
通讯作者：
Zhao, You-Yang
影响因子：
3.2
作者：
Eswarappa, Sandeepa M.;Pareek, Vidhi;Chakravortty, Dipshikha
通讯作者：
Chakravortty, Dipshikha
影响因子：
3.1
作者：
Lei, MG;Morrison, DC
通讯作者：
Morrison, DC