Molecular profiling reveals synaptic release machinery in Merkel cells

Molecular profiling reveals synaptic release machinery in Merkel cells
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DOI:
10.1073/pnas.0406308101
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发表时间:
2004-10-05
影响因子:
11.1
通讯作者:
Lumpkin, EA
Lumpkin, EA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Haeberle, H;Fujiwara, M;Lumpkin, EA

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默克尔细胞-神经突复合体是启动温柔触摸感知的体感受体。表皮默克尔细胞在这些复合体中的作用是有争议的。为了探究默克尔细胞是否在遗传上被编程为可能参与触摸接收的可兴奋细胞,我们从触摸圆顶中纯化了默克尔细胞,并使用DNA微阵列比较了默克尔细胞和其他表皮细胞中的基因表达。我们确定了362默克尔细胞丰富的成绩单,包括神经元转录因子,突触前分子和离子通道亚基。皮肤切片的抗体染色显示,默克尔细胞对突触前蛋白具有免疫反应性,包括piccolo、Rab 3C、囊泡谷氨酸转运蛋白2和胆囊收缩素26-33。这些数据表明,默克尔细胞准备释放谷氨酸和神经肽。最后,通过使用Ca 2+成像,我们发现默克尔细胞具有L型和P/Q型电压门控Ca 2+通道,其已被证明触发突触处的囊泡释放。这些结果表明,默克尔细胞是可兴奋的细胞,并表明它们释放神经递质来塑造触摸敏感性。
Merkel cell-neurite complexes are somatosensory receptors that initiate the perception of gentle touch. The role of epidermal Merkel cells within these complexes is disputed. To ask whether Merkel cells are genetically programmed to be excitable cells that may participate in touch reception, we purified Merkel cells from touch domes and used DNA microarrays to compare gene expression in Merkel cells and other epidermal cells. We identified 362 Merkel-cell-enriched transcripts, including neuronal transcription factors, presynaptic molecules, and ion-channel subunits. Antibody staining of skin sections showed that Merkel cells are immunoreactive for presynaptic proteins, including piccolo, Rab3C, vesicular glutamate transporter 2, and cholecystokinin 26-33. These data indicate that Merkel cells are poised to release glutamate and neuropeptides. Finally, by using Ca2+ imaging, we discovered that Merkel cells have L- and P/Q-type voltage-gated Ca2+ channels, which have been shown to trigger vesicle release at synapses. These results demonstrate that Merkel cells are excitable cells and suggest that they release neurotransmitters to shape touch sensitivity.