AII amacrine cells discriminate between heterocellular and homocellular locations when assembling connexin36-containing gap junctions.

AII amacrine cells discriminate between heterocellular and homocellular locations when assembling connexin36-containing gap junctions.
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DOI:
10.1242/jcs.133066
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发表时间:
2014-03-15
影响因子:
4
通讯作者:
Hormuzdi SG
Hormuzdi SG
中科院分区:
生物学2区
文献类型:
--
作者:
Meyer A;Hilgen G;Dorgau B;Sammler EM;Weiler R;Monyer H;Dedek K;Hormuzdi SG

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电突触(缝隙连接)在神经元之间快速传递信号,由连接蛋白组成。在神经元中,连接蛋白36(Cx 36)是最丰富的同种型;然而,含Cx 36的电突触的形成机制尚不清楚。我们专注于同细胞和异细胞间隙连接形成的AII无长突细胞,一个关键的interneuron在所有哺乳动物视网膜。在缺乏天然Cx 36但表达在C-末端标记有增强的绿色荧光蛋白的变体(KO-Cx 36-EGFP)的小鼠中,AII细胞和ON锥双极细胞之间形成的异细胞间隙连接是完全功能性的,而两个AII细胞之间不形成同细胞间隙连接。示踪剂注射到AII无长突细胞蔓延到ON锥双极细胞,但被排除在其他AII细胞。在KO-Cx 36-EGFP基因型的AII细胞上重建Cx 36-EGFP簇证实了簇的数量减少,但平均大小没有减少-正如缺乏电突触子集的AII细胞所预期的那样。我们的研究表明,一些神经元表现出至少两个歧视性的机制组装Cx 36。我们认为,采用不同的间隙连接形成机制可以提供一种手段,细胞调节其间隙连接在靶细胞特异性的方式,即使这些连接包含相同的连接蛋白。
Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap junctions formed by an AII amacrine cell, a key interneuron found in all mammalian retinas. In mice lacking native Cx36 but expressing a variant tagged with enhanced green fluorescent protein at the C-terminus (KO-Cx36-EGFP), heterocellular gap junctions formed between AII cells and ON cone bipolar cells are fully functional, whereas homocellular gap junctions between two AII cells are not formed. A tracer injected into an AII amacrine cell spreads into ON cone bipolar cells but is excluded from other AII cells. Reconstruction of Cx36–EGFP clusters on an AII cell in the KO-Cx36-EGFP genotype confirmed that the number, but not average size, of the clusters is reduced – as expected for AII cells lacking a subset of electrical synapses. Our studies indicate that some neurons exhibit at least two discriminatory mechanisms for assembling Cx36. We suggest that employing different gap-junction-forming mechanisms could provide the means for a cell to regulate its gap junctions in a target-cell-specific manner, even if these junctions contain the same connexin.
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