| Title | Tuning the Size of Large Dense-Core Vesicles and Quantal Neurotransmitter Release via Secretogranin II Liquid-Liquid Phase Separation |
| Authors | Lin, Zhaohan Li, Yinglin Hang, Yuqi Wang, Changhe Liu, Bing Li, Jie Yin, Lili Jiang, Xiaohan Du, Xingyu Qiao, Zhongjun Zhu, Feipeng Zhang, Zhe Zhang, Quanfeng Zhou, Zhuan |
| Affiliation | Peking Univ, Peking Tsinghua Ctr Life Sci, Coll Future Technol, Inst Mol Med,State Key Lab Membrane Biol, Beijing 100871, Peoples R China Peking Univ, Peking Tsinghua Ctr Life Sci, Coll Future Technol, Inst Mol Med,Beijing Key Lab Cardiometab Mol Med, Beijing 100871, Peoples R China Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing 100871, Peoples R China |
| Keywords | CHROMOGRANIN-A DEFICIENCY SECRETORY GRANULES CHROMAFFIN CELLS TARGETED ABLATION NEUROPEPTIDE-Y CALCIUM EXOCYTOSIS PROTEIN EXPRESSION STORAGE |
| Issue Date | Jul-2022 |
| Publisher | ADVANCED SCIENCE |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/649722 |
| DOI | 10.1002/advs.202202263 |
| Indexed | SCI(E) |
| Appears in Collections: | 分子医学研究所 膜生物学国家重点实验室 心理与认知科学学院 |
