Fantastic control of brain activity needs fast and effective neurotransmitter release. A key factor in his process is synaptic vesicle (SV), which is filled with neurotransmitters and stored at far neuronal terminals. Exocytosis of SVs releases neurotransmitters to engage postsynaptic responses and thus drive neuronal network communication. Very interestingly, SV endocytosis is tightly coupled to exocytosis and occurs immediately after exocytosis, which is thought as the key mechanism that sustains a balance of SV proteins at the release site, plasma membrane equilibrium, SV identity, and SV pool quantity. Most interestingly, several modes of SV endocytosis have been discovered and act differentially in terms of formation time, location, and morphology. Importantly, accumulative evidence has revealed that dysfunctional SV endocytosis is linked to human neurological diseases. In my lab, we have been interested in a synaptic vesicle-associated Ca²⁺ channel, called Flower. Our studies have shown that Flower controls synaptic vesicle exocytosis and endocytosis coupling. In addition, Flower has stimulus-dependent functions to balance clathrin-mediated endocytosis, induced under mild activity stimulation conditions, and bulk endocytosis, a predominant mode triggered by strong stimulations. Most recent work further established interplay between Flower and phospholipids in presynaptic plasma membrane as the spatiotemporal cue for boosting bulk endocytosis. Now, we are very excited to further investigate following questions.

1. The mechanism underlying coupling control of exocytosis to endocytosis by Flower.
2. Structural study on channel-dependent and channel-independent functions of Flower.
3. The role of Flower in mouse central brain.
4. The disease relevance of human associated Flower mutations.
5. Establishment of a systematic protein interaction network in SV endocytosis via in vivo APEX2 proteomics.