Persistence of quantal synaptic vesicle recycling in virtual absence of dynamins

IF 4.4 2区 医学 Q1 NEUROSCIENCES Journal of Physiology-London Pub Date : 2024-08-14 DOI:10.1113/JP286711
Olusoji A. T. Afuwape, Natali L. Chanaday, Merve Kasap, Lisa M. Monteggia, Ege T. Kavalali
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Abstract

Dynamins are GTPases required for pinching vesicles off the plasma membrane once a critical curvature is reached during endocytosis. Here, we probed dynamin function in central synapses by depleting all three dynamin isoforms in postnatal hippocampal neurons down to negligible levels. We found a decrease in the propensity of evoked neurotransmission as well as a reduction in synaptic vesicle numbers. Recycling of synaptic vesicles during spontaneous or low levels of evoked activity were largely impervious to dynamin depletion, while retrieval of synaptic vesicle components at higher levels of activity was partially arrested. These results suggest the existence of balancing dynamin-independent mechanisms for synaptic vesicle recycling at central synapses. Classical dynamin-dependent mechanisms are not essential for retrieval of synaptic vesicle proteins after quantal single synaptic vesicle fusion, but they become more relevant for membrane retrieval during intense, sustained neuronal activity.

Key points

  • Loss of dynamin 2 does not impair synaptic transmission.
  • Loss of all three dynamin isoforms mostly affects evoked neurotransmission.
  • Excitatory synapse function is more susceptible to dynamin loss.
  • Spontaneous neurotransmission is only mildly affected by loss of dynamins.
  • Single synaptic vesicle endocytosis is largely dynamin independent.

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在几乎没有动态蛋白的情况下,量子突触囊泡循环依然存在。
达因明是一种 GTP 酶,当内吞过程中达到临界曲率时,它需要将囊泡从质膜上捏下来。在这里,我们通过将出生后海马神经元中的所有三种达因明异构体消耗至可忽略不计的水平,来探究达因明在中枢突触中的功能。我们发现诱发神经传递的倾向性降低了,突触小泡的数量也减少了。在自发或低水平的诱发活动中,突触小泡的再循环在很大程度上不受动态素耗竭的影响,而在较高水平的活动中,突触小泡成分的回收则部分受阻。这些结果表明,中枢突触的突触囊泡再循环存在着不依赖于达维素的平衡机制。经典的依赖达明敏的机制对于突触囊泡蛋白在单个突触囊泡融合后的回收并不是必不可少的,但在神经元剧烈、持续的活动中,它们对于膜的回收变得更加重要。要点缺失达因明 2 不会损害突触传递。三种达因明异构体的缺失主要影响诱发神经传递。兴奋性突触功能更易受动态素缺失的影响。自发神经传递只受到动态蛋白缺失的轻微影响。单突触囊泡的内吞在很大程度上与动态素无关。
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来源期刊
Journal of Physiology-London
Journal of Physiology-London 医学-神经科学
CiteScore
9.70
自引率
7.30%
发文量
817
审稿时长
2 months
期刊介绍: The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew. The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.
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