Dynamin 1 (dyn1) is required for clathrin-mediated endocytosis in most secretory (neuronal and neuroendocrine) cells. There are two modes of Ca 2ϩ -dependent catecholamine release from single dense-core vesicles: full-quantal (quantal) and subquantal in adrenal chromaffin cells, but their relative occurrences and impacts on total secretion remain unclear. To address this fundamental question in neurotransmission area using both sexes of animals, here we report the following: (1) dyn1-KO increased quantal size (QS, but not vesicle size/content) by Ն250% in dyn1-KO mice; (2) the KO-increased QS was rescued by dyn1 (but not its deficient mutant or dyn2); (3) the ratio of quantal versus subquantal events was increased by KO; (4) following a release event, more protein contents were retained in WT versus KO vesicles; and (5) the fusion pore size (d p ) was increased from Յ9 to Ն9 nm by KO. Therefore, Ca 2ϩ -induced exocytosis is generally a subquantal release in sympathetic adrenal chromaffin cells, implying that neurotransmitter release is generally regulated by dynamin in neuronal cells. Ca 2ϩ -dependent neurotransmitter release from a single vesicle is the primary event in all neurotransmission, including synaptic/ neuroendocrine forms. To determine whether Ca 2ϩ -dependent vesicular neurotransmitter release is "all-or-none" (quantal), we provide compelling evidence that most Ca 2ϩ -induced secretory events occur via the subquantal mode in native adrenal chromaffin cells. This subquantal release mode is promoted by dynamin 1, which is universally required for most secretory cells, including neurons and neuroendocrine cells. The present work with dyn1-KO mice further confirms that Ca 2ϩ -dependent transmitter release is mainly via subquantal mode, suggesting that subquantal release could be also important in other types of cells.

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Our findings suggest that depolarisation-induced Ca(2+) influx plays dual roles in regulating exocytosis in rat pancreatic beta cells by triggering vesicle fusion and replenishing the vesicle pool to support sustained insulin release. Therefore, Ca(2+) influx may be important for glucose-stimulated insulin secretion.

Large dense‐core vesicles (LDCVs) are larger in volume than synaptic vesicles, and are filled with multiple neuropeptides, hormones, and neurotransmitters that participate in various physiological processes. However, little is known about the mechanism determining the size of LDCVs. Here, it is reported that secretogranin II (SgII), a vesicle matrix protein, contributes to LDCV size regulation through its liquid–liquid phase separation in neuroendocrine cells. First, SgII undergoes pH‐dependent polymerization and the polymerized SgII forms phase droplets with Ca2+ in vitro and in vivo. Further, the Ca2+‐induced SgII droplets recruit reconstituted bio‐lipids, mimicking the LDCVs biogenesis. In addition, SgII knockdown leads to significant decrease of the quantal neurotransmitter release by affecting LDCV size, which is differently rescued by SgII truncations with different degrees of phase separation. In conclusion, it is shown that SgII is a unique intravesicular matrix protein undergoing liquid–liquid phase separation, and present novel insights into how SgII determines LDCV size and the quantal neurotransmitter release.

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Giβγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y12(D76/D127) → Giβγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.

Delicate control of the precipitate/supernatant ratio in the precursor suspension during liquid-phase synthesis of Li7P3S11 provides information on how the morphology of the impurities affect the ionic conductivity. In this work, the influence of the precipitate/supernatant ratio on the phase structure, the morphology and the ionic conductivity of Li7P3S11 prepared in acetonitrile is studied. It is revealed that in the supernatant-excess region, the excess amorphous "Li2S•P2S5" finally turns into a poorly ionic conductive phase Li4P2S6 which wraps Li7P3S11 particles, increasing the interfacial resistance. In the precipitate-excess region, a thio-LISICON III phase turned from the excess precipitate tends to stay within Li7P3S11 particles, and therefore its negative influence on the total ionic conductivity is not evident. Consequently, a slight composition shift into the precipitate-excess region benefits the ionic conductivity of the resultant solid electrolyte.

Neonicotinoid and fipronil insecticides have been consumed worldwide, particularly in China. There is a growing interest in the environmental research community about the occurrence, fates, sources, and risks of neonicotinoids...

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