Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons

Cell-specific expression of connexins and evidence of restricted gap junctional coupling between glial cells and between neurons
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DOI:
10.1523/jneurosci.21-06-01983.2001
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发表时间:
2001-03-15
影响因子:
5.3
通讯作者:
Nagy, JI
Nagy, JI
中科院分区:
医学1区
文献类型:
--
作者:
Rash, JE;Yasumura, T;Nagy, JI

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间隙连接的跨膜连接蛋白在细胞外连接,形成细胞间离子和小分子交换的通道。CNS中缝隙连接偶联的两个主要假设如下:(1)神经元和神经胶质之间发生广义偶联,其中一些连接蛋白在神经元和神经胶质中表达,和(2)细胞间连接偶联限于特定偶联伴侣,其中不同连接蛋白在每种细胞类型中表达。人们一致认为间隙连接将神经元与神经元连接,将星形胶质细胞与少突胶质细胞、室管膜细胞和其他星形胶质细胞连接。然而,尚未解决的是间隙连接的存在和程度,发生在少突胶质细胞之间,少突胶质细胞和神经元之间,星形胶质细胞和神经元之间。使用光学显微镜免疫细胞化学和冷冻断裂复制免疫金标记的成年大鼠中枢神经系统,我们研究了是否四个最好的特征中枢神经系统连接蛋白是每个存在于一个或多个细胞类型,是否少突胶质细胞也共享间隙连接与其他少突胶质细胞或神经元,以及是否星形胶质细胞共享间隙连接与神经元。连接蛋白32(Cx32)仅存在于少突胶质细胞质膜的间隙连接中,Cx30和Cx43仅存在于星形胶质细胞膜中,Cx36仅存在于神经元中。少突胶质细胞仅与星形胶质细胞共享细胞间间隙连接,每个少突胶质细胞与其他少突胶质细胞分离,除非通过星形胶质细胞中介。最后,神经元仅与其他神经元共享间隙连接,而不与神经胶质细胞共享。因此,CNS的不同细胞类型表达不同的连接蛋白,其定义了神经元与神经胶质细胞间隙连接通讯的不同途径。
The transmembrane connexin proteins of gap junctions link extracellularly to form channels for cell-to-cell exchange of ions and small molecules. Two primary hypotheses of gap junction coupling in the CNS are the following: (1) generalized coupling occurs between neurons and glia, with some connexins expressed in both neurons and glia, and (2) intercellular junctional coupling is restricted to specific coupling partners, with different connexins expressed in each cell type. There is consensus that gap junctions link neurons to neurons and astrocytes to oligodendrocytes, ependymocytes, and other astrocytes. However, unresolved are the existence and degree to which gap junctions occur between oligodendrocytes, between oligodendrocytes and neurons, and between astrocytes and neurons. Using light microscopic immunocytochemistry and freeze-fracture replica immunogold labeling of adult rat CNS, we investigated whether four of the best-characterized CNS connexins are each present in one or more cell types, whether oligodendrocytes also share gap junctions with other oligodendrocytes or with neurons, and whether astrocytes share gap junctions with neurons. Connexin32 (Cx32) was found only in gap junctions of oligodendrocyte plasma membranes, Cx30 and Cx43 were found only in astrocyte membranes, and Cx36 was only in neurons. Oligodendrocytes shared intercellular gap junctions only with astrocytes, with each oligodendrocyte isolated from other oligodendrocytes except via astrocyte intermediaries. Finally, neurons shared gap junctions only with other neurons and not with glial cells. Thus, the different cell types of the CNS express different connexins, which define separate pathways for neuronal versus glial gap junctional communication.