Department of Anesthesiology, University of California, San Diego, La Jolla, CA 92093, USA.
Mol Cell Neurosci. 2013 Sep;56:283-97. doi: 10.1016/j.mcn.2013.07.002. Epub 2013 Jul 10.
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 (Cavs), membrane/lipid raft proteins, are expressed in inflammatory cells, yet the role of caveolin isoforms in microglia physiology is debatable. We propose that 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 (CVs) 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.
小胶质细胞是一种分支状细胞，作为中枢神经系统 (CNS) 的守护者，能够增殖、迁移和产生炎症细胞因子。在非病理状态下，这些细胞表现出分支状形态，其突起与神经元和星形胶质细胞交织在一起。在病理状态下，它们获得圆形阿米巴样形态和增殖和迁移能力。这种形态变化需要细胞骨架的重排。微管和肌动蛋白聚合状态的分子控制点仍在研究中。窖蛋白 (Cavs) 是一种膜/脂筏蛋白，在炎症细胞中表达，但 Cav 同工型在小胶质细胞生理学中的作用仍存在争议。我们提出，窖蛋白为细胞骨架动力学的调节提供了一个必要的控制点，并因此研究了窖蛋白在小胶质细胞生物学中的作用。我们检测到 Cav-1 和 Cav-3 的 mRNA 和蛋白。在小胶质细胞非激活状态下，Cav-1 蛋白明显减少，定位于质膜 (PM) 和细胞质小泡 (CV)，而激活的 (阿米巴样) 小胶质细胞则表现出 Cav-1 表达增加。相比之下，Cav-3 在非激活状态下高度表达，定位于细胞突起和核周区，并在激活的阿米巴样小胶质细胞中检测到。在激活或非激活状态下对细胞骨架的药理学操作改变了窖蛋白的表达。此外，增加的 Cav-1 表达也增加了线粒体呼吸，这表明在促进形态变化的细胞代谢中可能具有调节作用。这些发现强烈表明，小胶质细胞形态和活性的调节部分归因于窖蛋白同工型，为中枢神经系统损伤或疾病提供了有前途的新的治疗靶点。
