Molecular scaffolds underpinning macroglial polarization: an analysis of retinal Müller cells and brain astrocytes in mouse.
Molecular scaffolds underpinning macroglial polarization: an analysis of retinal Müller cells and brain astrocytes in mouse.
复制标题
DOI：
10.1002/glia.22416
复制
发表时间：
2012-12
期刊：
影响因子：
6.2
通讯作者：
Nagelhus, Erlend A.
中科院分区：
文献类型：
--
作者：
Enger, Rune;Gundersen, Georg Andreas;Haj-Yasein, Nadia Nabil;Eilert-Olsen, Martine;Thoren, Anna Elisabeth;Vindedal, Gry Fluge;Petersen, Petur Henry;Skare, Oivind;Nedergaard, Maiken;Ottersen, Ole Petter;Nagelhus, Erlend A.
大胶质细胞的关键作用与特殊的膜结构域密不可分。血管周围终足膜引起了特别的关注，因为该结构域包含独特的水通道蛋白-4 （AQP4）和其他通道蛋白的补体，使其与突触周围膜区分开来。最近的研究表明，在包括颞叶癫痫和阿尔茨海默病在内的许多疾病中，大胶质细胞的极化丢失。我们需要更好地理解星形胶质细胞极化的分子基础，特别是当涉及到营养不良蛋白相关蛋白复合物（DAPC）的意义时。本研究采用免疫荧光和免疫金细胞化学方法，以AQP4为标记物，分析了视网膜大胶质细胞和大脑皮层、齿状回和小脑三个区域血管周围终足的分子支架结构。与脑星形胶质细胞相比，m<s:1> ller细胞（一类视网膜大胶质细胞）的支架蛋白-肌营养不良蛋白和α-syntrophin（一种DAPC蛋白）的密度较低，但AQP4的水平较高。与此一致的是，肌营养不良蛋白或α-syntrophin的耗竭虽然会导致脑星形胶质细胞端足膜AQP4的急剧损失，但对<s:1> ller细胞端足膜AQP4池的影响分别只有适度或不显著。此外，与α-syntrophin靶向缺失相比，肌营养不良蛋白缺失对脑大胶质细胞极化的影响较小，而视网膜大胶质细胞极化的影响则相反。这些数据表明，血管周围终足的分子支架比以前假设的更复杂，并且大胶质细胞在决定其极化的机制方面是异质的。
Key roles of macroglia are inextricably coupled to specialized membrane domains. The perivascular endfoot membrane has drawn particular attention, as this domain contains a unique complement of aquaporin-4 (AQP4) and other channel proteins that distinguishes it from perisynaptic membranes. Recent studies indicate that the polarization of macroglia is lost in a number of diseases, including temporal lobe epilepsy and Alzheimer’s disease. A better understanding is required of the molecular underpinning of astroglial polarization, particularly when it comes to the significance of the dystrophin associated protein complex (DAPC). Here we employ immunofluorescence and immunogold cytochemistry to analyze the molecular scaffolding in perivascular endfeet in macroglia of retina and three regions of brain (cortex, dentate gyrus and cerebellum), using AQP4 as a marker. Compared with brain astrocytes, Müller cells (a class of retinal macroglia) exhibit lower densities of the scaffold proteins dystrophin and α-syntrophin (a DAPC protein), but higher levels of AQP4. In agreement, depletion of dystrophin or α-syntrophin – while causing a dramatic loss of AQP4 from endfoot membranes of brain astrocytes – had only modest or insignificant effect, respectively, on the AQP4 pool in endfoot membranes of Müller cells. Also, while polarization of brain macroglia was less affected by dystrophin depletion than by targeted deletion of α-syntrophin, the reverse was true for retinal macroglia. These data indicate that the molecular scaffolding in perivascular endfeet is more complex than previously assumed and that macroglia are heterogeneous with respect to the mechanisms that dictate their polarization.
登录
查看更多内容
影响因子：
4.8
作者：
Connors, NC;Adams, ME;Kofuji, P
通讯作者：
Kofuji, P
DOI：
10.1073/pnas.0409308102
发表时间：
2005-01-25
影响因子：
11.1
作者：
Eid, T;Lee, TSW;de Lanerolle, NC
通讯作者：
de Lanerolle, NC
影响因子：
7.8
作者：
Peters, MF;Adams, ME;Froehner, SC
通讯作者：
Froehner, SC
DOI：
10.1016/j.nurt.2010.07.006
发表时间：
2010-10
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Kimelberg HK;Nedergaard M
通讯作者：
Nedergaard M
DOI：
10.1073/pnas.241508198
发表时间：
2001-11-20
影响因子：
11.1
作者：
Neely, JD;Amiry-Moghaddam, M;Adams, ME
通讯作者：
Adams, ME