Afuwape Olusoji A T, Chanaday Natali L, Kasap Merve, Monteggia Lisa M, Kavalali Ege T
Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
J Physiol. 2024 Aug 14. doi: 10.1113/JP286711.
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.
发动蛋白是一种GTP酶,在内吞作用过程中,一旦质膜达到临界曲率,它对于从质膜上掐断囊泡是必需的。在此,我们通过将出生后海马神经元中的所有三种发动蛋白亚型消耗至可忽略不计的水平,来探究中枢突触中的发动蛋白功能。我们发现诱发神经传递的倾向降低,以及突触囊泡数量减少。在自发或低水平诱发活动期间,突触囊泡的再循环在很大程度上不受发动蛋白消耗的影响,而在较高水平活动时,突触囊泡成分的回收则部分受阻。这些结果表明,中枢突触中存在平衡的、不依赖发动蛋白的突触囊泡再循环机制。经典的依赖发动蛋白的机制对于量子单突触囊泡融合后突触囊泡蛋白的回收并非必不可少,但在强烈、持续的神经元活动期间,它们对于膜回收变得更加重要。要点:发动蛋白2的缺失不会损害突触传递。所有三种发动蛋白亚型的缺失主要影响诱发神经传递。兴奋性突触功能对发动蛋白缺失更敏感。自发神经传递仅受到发动蛋白缺失的轻微影响。单突触囊泡内吞作用在很大程度上不依赖发动蛋白。