Synaptic-like vesicles and candidate transduction channels in mechanosensory terminals.
Synaptic-like vesicles and candidate transduction channels in mechanosensory terminals.
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DOI：
10.1111/joa.12337
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发表时间：
2015-08
影响因子：
2.4
通讯作者：
Bewick GS
中科院分区：
文献类型：
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作者：
Bewick GS
本文总结了与Bob Banks合作的前15年令人兴奋和非常愉快的进展。我们的合作开始于我联系他时，他给了我一个意想不到的观察结果，一种用于标记传出末梢的突触囊泡膜回收的染料也标记了肌梭传入末梢。这一观察结果导致重新发现了存在于所有脊椎动物初级机械感觉神经末梢中的小透明囊泡系统。这些突触样囊泡（SLV）一直是，并将继续是我们工作的主要焦点。本文介绍了我们的特性和功能的意义，这些SLV，结合我们的互补技能：鲍勃的技术专长和mechanosensation与我的经验，突触囊泡和苯乙烯基吡啶染料的发展，其中最广泛使用的是FM 1 -43的mechanosensation儿科知识。在此过程中，我们发现SLV似乎是组成性谷氨酸分泌系统的一部分，该系统是维持纺锤体末端拉伸敏感性所必需的。谷氨酸激活一种与磷脂酶D激活相关的极不寻常的谷氨酸受体，我们称之为PLD-mGluR。它有一个完全不同的药理学首次描述在海马体近20年前，但像SLV首次描述超过50年前，一直很少研究。然而，我们的证据和文献检索表明，这种谷氨酸/SLV/PLD-mGluR系统是机械感觉末梢的普遍特征，并且至少对于纺锤体而言，对于维持机械感觉功能至关重要。本文总结了这个系统如何整合与经典模型的机械敏感通道的纺锤体和其他mechanosensory神经末梢，包括毛囊传入和压力感受器控制血压。最后，在这个时候，有必要显示翻译的相关性，我描述了这个迷人的系统实际上可能是一个有用的治疗药物靶点的临床条件，如高血压和肌肉痉挛。这是一个迷人的15年的旅程，与鲍勃合作，以及有一个精明的科学头脑，也是一个伟大的爱好者，激励者和朋友。我希望这个令人兴奋和愉快的旅程将持续到未来。
This article summarises progress to date over an exciting and very enjoyable first 15 years of collaboration with Bob Banks. Our collaboration began when I contacted him with (to me) an unexpected observation that a dye used to mark recycling synaptic vesicle membrane at efferent terminals also labelled muscle spindle afferent terminals. This observation led to the re-discovery of a system of small clear vesicles present in all vertebrate primary mechanosensory nerve terminals. These synaptic-like vesicles (SLVs) have been, and continue to be, the major focus of our work. This article describes our characterisation of the properties and functional significance of these SLVs, combining our complementary skills: Bob’s technical expertise and encyclopaedic knowledge of mechanosensation with my experience of synaptic vesicles and the development of the styryl pyridinium dyes, of which the most widely used is FM1-43. On the way we have found that SLVs seem to be part of a constitutive glutamate secretory system necessary to maintain the stretch-sensitivity of spindle endings. The glutamate activates a highly unusual glutamate receptor linked to phospholipase D activation, which we have termed the PLD-mGluR. It has a totally distinct pharmacology first described in the hippocampus nearly 20 years ago but, like the SLVs that were first described over 50 years ago, has since been little researched. Yet, our evidence and literature searches suggest this glutamate/SLV/PLD-mGluR system is a ubiquitous feature of mechanosensory endings and, at least for spindles, is essential for maintaining mechanosensory function. This article summarises how this system integrates with the classical model of mechanosensitive channels in spindles and other mechanosensory nerve terminals, including hair follicle afferents and baroreceptors controlling blood pressure. Finally, in this time when there is an imperative to show translational relevance, I describe how this fascinating system might actually be a useful therapeutic drug target for clinical conditions such as hypertension and muscle spasticity. This has been a fascinating 15-year journey in collaboration with Bob who, as well as having an astute scientific mind, is also a great enthusiast, motivator and friend. I hope this exciting and enjoyable journey will continue well into the future.