Abortive infection of bat fibroblasts with SARS-CoV-2.

Bats are tolerant to highly pathogenic viruses such as Marburg, Ebola, and Nipah, suggesting the presence of a unique immune tolerance toward viral infection. Here, we compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of human and bat () pluripotent cells and fibroblasts. Since bat cells do not express an angiotensin-converting enzyme 2 (ACE2) receptor that allows virus infection, we transduced the human ACE2 (hA) receptor into the cells and found that transduced cells can be infected with SARS-CoV-2.

Distinct active zone protein machineries mediate Ca channel clustering and vesicle priming at hippocampal synapses.

Action potentials trigger neurotransmitter release at the presynaptic active zone with spatiotemporal precision. This is supported by protein machinery that mediates synaptic vesicle priming and clustering of Ca2 Ca channels nearby. One model posits that scaffolding proteins directly tether vesicles to Ca2s; however, here we find that at mouse hippocampal synapses, Ca2 clustering and vesicle priming are executed by separate machineries.

Molecular definition of distinct active zone protein machineries for Ca channel clustering and synaptic vesicle priming.

Action potentials trigger neurotransmitter release with minimal delay. Active zones mediate this temporal precision by co-organizing primed vesicles with Ca2 Ca channels. The presumed model is that scaffolding proteins directly tether primed vesicles to Ca2s.

Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones.

Active zones consist of protein scaffolds that are tightly attached to the presynaptic plasma membrane. They dock and prime synaptic vesicles, couple them to voltage-gated Ca channels, and direct neurotransmitter release toward postsynaptic receptor domains. Simultaneous RIM + ELKS ablation disrupts these scaffolds, abolishes vesicle docking, and removes active zone-targeted Munc13, but some vesicles remain releasable.