| First Author | Park SJ | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 4 | Pages | 101000 |
| PubMed ID | 32252022 | Mgi Jnum | J:306957 |
| Mgi Id | MGI:6718172 | Doi | 10.1016/j.isci.2020.101000 |
| Citation | Park SJ, et al. (2020) Inositol Pyrophosphate Metabolism Regulates Presynaptic Vesicle Cycling at Central Synapses. iScience 23(4):101000 |
| abstractText | The coordination of synaptic vesicle exocytosis and endocytosis supports neurotransmitter release from presynaptic terminals. Although inositol pyrophosphates, such as 5-diphosphoinositol pentakisphosphate (5-IP7), are versatile signaling metabolites in many biological events, physiological actions of 5-IP7 on synaptic membrane vesicle trafficking remain unclear. Here, we investigated the role of 5-IP7 in synaptic transmission in hippocampal brain slices from inositol hexakisphosphate kinase 1 (Ip6k1)-knockout mice. We found that presynaptic release probability was significantly increased in Ip6k1-knockout neurons, implying enhanced activity-dependent synaptic vesicle exocytosis. Expression of wild-type but not catalytically inactive IP6K1 in the Ip6k1-knockout hippocampus restored the altered presynaptic release probability. Moreover, Ip6k1-knockout neurons were insensitive to folimycin, a vacuolar ATPase inhibitor, and dynasore, a dynamin inhibitor, suggesting marked impairment in synaptic endocytosis during exocytosis. Our findings collectively establish that IP6K1 and its product, 5-IP7, act as key physiological determinants for inhibition of presynaptic vesicle exocytosis and stimulation of endocytosis at central synapses. |
