뇌 이노시톨 다인산 대사체중 하나인 5-IP7의 신경전달물질 분비조절관련 신규 신호전달기능을 규명하여 PNAS에 게재함. 연세대학교-IBS 윤태영 교수, 경희대학교 김성현 교수 연구진과의 공동연구를 통하여 5-IP7 대사체가 신경전달을 매개하는 시냅토태그민-1 단백질에 직접적으로 결합하여 활성을 강력하게 억제함으로써 신경전달물질 분비를 정교하게 조절함을 밝힘.
Inositol phosphates (IP) have long been known to be negative regulators of synaptic exocytosis, but the function of diphosphoinositol pentakisphosphate (IP7) has remained elusive. We found that overexpression and depletion of inositol hexakisphosphate (IP6) kinase in PC12 cells or hippocampal neurons led to a reduction and increase in neurotransmitter release, respectively. Biophysical assays revealed that 5-IP7 inhibited calcium-induced synaptic membrane fusion at a concentration one order of magnitude lower than that required for IP6. We further elucidated the molecular mechanism responsible for 5-IP7 actions, demonstrating that 5-IP7 directly bound with high affinity to synaptotagmin 1 (Syt1), a calcium sensor in cellular exocytosis, and suppressed its fusogenic activity. Thus, our data propose 5-IP7 as a potent inhibitor of Syt1 actions on calcium-mediated synaptic vesicle fusion.