Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex.
Chemical synapses without synaptic vesicles: Purinergic neurotransmission through a CALHM1 channel-mitochondrial signaling complex.
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DOI：
10.1126/scisignal.aao1815
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发表时间：
2018-05-08
影响因子：
7.3
通讯作者：
Finger TE
中科院分区：
文献类型：
--
作者：
Romanov RA;Lasher RS;High B;Savidge LE;Lawson A;Rogachevskaja OA;Zhao H;Rogachevsky VV;Bystrova MF;Churbanov GD;Adameyko I;Harkany T;Yang R;Kidd GJ;Marambaud P;Kinnamon JC;Kolesnikov SS;Finger TE
连接味觉受体细胞和味觉神经的突触显示出不同寻常的功能特性，表明其具有独特的结构组织。神经系统中的传统化学突触涉及突触前含有神经递质的囊泡的积累，这些囊泡在激活后融合到质膜上释放神经递质，从而激活突触后细胞上的受体。在味蕾中，味觉受体细胞（II型感觉细胞）没有表现出传统的突触特征，但仍然表现出传入神经递质ATP的调节释放——不是通过突触囊泡与膜的融合，而是通过一个大孔、电压门控通道CALHM1。免疫组织化学显示CALHM1紧密定位于受体细胞和感觉神经纤维之间的接触点。超微结构和超分辨率光镜显示CALHM1通道总是与距离突触前膜20-40 nm的独特的大（1-2μm）线粒体相关。线粒体呼吸链的药物破坏限制了味觉细胞释放ATP的能力，这表明释放ATP的直接来源是线粒体，而不是整个细胞质的ATP池。这些大的线粒体既可以作为可释放ATP的储存库，也可以作为合成的场所。大线粒体与显示CALHM1的膜区域并置也定义了一个受限的隔室，限制了非选择性CALHM1通道打开时Ca2+的流入。这些发现揭示了一个独特的细胞器特征和功能组织，在没有突触囊泡的情况下，嘌呤能信号的调控和局灶释放。
The synapse linking taste receptor cells to the taste nerves shows unusual functional properties suggestive of a unique structural organization. Conventional chemical synapses in the nervous system involve a presynaptic accumulation of neurotransmitter-containing vesicles, which upon activation, fuse to the plasma membrane to release neurotransmitter that activates receptors on the postsynaptic cell. In taste buds, taste receptor cells (Type II sensory cells) exhibit no conventional synaptic features but nonetheless show regulated release of their afferent neurotransmitter, ATP -- not via fusion of synaptic vesicles to the membrane but rather through a large-pore, voltage-gated channel, CALHM1. Immunohistochemistry reveals that CALHM1 is tightly localized to points of contact between the receptor cells and sensory nerve fibers. Ultrastructural and super-resolution light microscopy show that the CALHM1 channels always are associated with distinctive, large (1–2μm) mitochondria spaced 20–40 nm from the presynaptic membrane. Pharmacological disruption of the mitochondrial respiratory chain limits the ability of the taste cells to release ATP suggesting that the immediate source of released ATP is the mitochondrion rather than a global cytoplasmic pool of ATP. These large mitochondria may serve as both a reservoir of releasable ATP as well as the site of synthesis. The juxtaposition of the large mitochondrion to the areas of membrane displaying CALHM1 also define a restricted compartment that limits the influx of Ca2+ upon opening of the non-selective CALHM1 channels. These findings reveal a distinctive organelle signature and functional organization for regulated, focal release of purinergic signals in the absence of synaptic vesicles.
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味觉的细胞生物学。
影响因子：
7.8
作者：
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通讯作者：
Roper, Stephen D.
DOI：
10.1073/pnas.1204023109
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