Synaptotagmins (Syts) are well-established primary Ca2+ sensors to initiate presynaptic neurotransmitter release. They also play critical roles in the docking, priming, and fusion steps of exocytosis, as well as the tightly coupled exo-endocytosis, in presynapses. A recent study by Awasthi and others (2019) shows that Syt3 Ca2+-dependently modulates the postsynaptic receptor endocytosis and thereby promotes the long-term depression (LTD) and the decay of long-term potentiation (LTP). This work highlights the importance of Syt3 in modulating long-term synaptic plasticity and, importantly, extends the function of Syt proteins from presynaptic neurotransmitter release to a new promising postsynaptic receptor internalization.

Significance Precise and efficient coupling of endocytosis to exocytosis is critical for neurotransmission. The activity-dependent facilitation of endocytosis has been well established for efficient membrane retrieval; however, whether neural activity clamps endocytosis to avoid excessive membrane retrieval remains debatable with the mechanisms largely unknown. The present work provides compelling evidence that synaptotagmin-1 (Syt1) functions as a primary bidirectional Ca 2+ sensor to promote slow, small-sized clathrin-mediated endocytosis but inhibit the fast, large-sized bulk endocytosis during elevated neural activity, the disruption of which leads to inefficient vesicle recycling under mild stimulation but excessive membrane retrieval following sustained neurotransmission. Thus, Syt1 serves as a fine-tuning Ca 2+ sensor to ensure both efficient and precise coupling of endocytosis to exocytosis in response to different neural activities.

Two-component signal transduction systems (TCSs) play a major role in adaption and survival of microorganisms in a dynamic and sometimes dangerous environment. YycFG is an essential TCS for many Gram-positive bacteria, such as Bacillus subtilis, which regulates many important biological processes. However, its functional essentiality remains largely unknown. Here, we report several YycFG interacting proteins through coimmunoprecipitation (Co-IP) and mass spectrometry (MS) analyses. We engineered the B. subtilis genome by a knock-in approach to express YycG with a C-terminal Flag and YycF with an N-terminal HA tag. Immunoprecipitated fractions using anti-Flag or anti-HA agarose were subjected to MS analyses. A total of 41 YycG interacting proteins and four YycF interacting proteins were identified, most of which are involved in cellular metabolic processes, including cell wall synthesis and modification. The interactions of YycG with AsnB and FabL, as examples, were further validated in vitro. This study provided a clue that YycFG may be directly involved in regulation of bacterial central metabolic pathways. K E Y W O R D S YycFG, two-component system, protein-protein interactions, coimmunoprecipitation, mass spectrometry

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