Ca2+ sensor proteins in spontaneous release and synaptic plasticity: Limited contribution of Doc2c, rabphilin-3a and synaptotagmin 7 in hippocampal glutamatergic neurons

Role of Rph3A in brain injury induced by experimental cerebral ischemia‐reperfusion model in rats

“…They share the same conserved tandem C 2 domain structure but have different functions in terms of subcellular location, Ca 2+ binding properties and protein interactions 37 . In a study of spontaneous release from hippocampal glutamatergic neurons, it was found that ablation of the Rph3A gene in the absence of Doc2 and removal of Rph3A resulted in an increased frequency of spontaneous release from glutamatergic neurons in neuron‐glia co‐cultures, suggesting that Rph3A may influence spontaneous release of glutamate from hippocampal neurons and play a regulatory role in the neuronal network 38 . An earlier study on the correlation between Rph3A and neurotransmitter release was carried out by Burns et al 28 , who found that presynaptic neurotransmitter release was inhibited after injection of recombinant full‐length bovine Rph3A into the giant presynaptic terminals of squid.…”

“…37 In a study of spontaneous release from hippocampal glutamatergic neurons, it was found that ablation of the Rph3A gene in the absence of Doc2 and removal of Rph3A resulted in an increased frequency of spontaneous release from glutamatergic neurons in neuron-glia co-cultures, suggesting that Rph3A may influence spontaneous release of glutamate from hippocampal neurons and play a regulatory role in the neuronal network. 38 An earlier study on the correlation between Rph3A and neurotransmitter release was carried out by Burns et al 28 , who found that presynaptic neurotransmitter release was inhibited after injection of recombinant full-length bovine Rph3A into the giant presynaptic terminals of squid. However, the exact mechanism by which Rph3A inhibits neurotransmitter release was not known until it was revealed that in PC12 cells, Rph3A can interact with synaptosomalassociated protein (SNAP25) during the cytosolic docking step.…”

The Structural Basis of Long-Term Potentiation in Hippocampal Synapses, Revealed by Electron Microscopy Imaging of Lanthanum-Induced Synaptic Vesicle Recycling

“…This may someday be explained by several different mechanisms: for example, by some sort of “stiffening” of the presynaptic membrane or by La+++ tending to “glue” the presynaptic membrane to the extracellular matrix, or possibly by blocking sodium and calcium entry through the presynaptic membrane, which may in some way directly slow down some aspect of the recycling process. Indeed, there is a large body of evidence, which suggests that clathrin-coated vesicle formation and/or synaptic vesicle recycling is somehow dependent on intracellular Ca ++ being at just the right level ( Henkel and Betz, 1995 ; Neale et al, 1999 ; Vogel et al, 1999 ; Teng and Wilkinson, 2003 ; Zefirov et al, 2006 ; Yao et al, 2009 ; Morton et al, 2015 ; Miyano et al, 2019 ; Bourgeois-Jaarsma et al, 2021 ; Jiang et al, 2021 ). In any case, it is abundantly clear from the present observations and from the past work that lanthanum somehow creates a greater imbalance between exocytosis and endocytosis than any other form of synaptic stimulation, and consequently, produces the most enhanced accumulation of synaptic vesicle membrane on the presynaptic surface, and thus, the greatest expansion of the presynaptic membrane.…”