Studies On The Mechanims Of Rab11-FIP3 In The Regulation Of Synaptic Plasticity

Rab GTPase plays roles of providing energy by transporting GTP primarily during membrane transport.The role of Rab kinase in vesicle transport is particularly prominent.Rab4,Rab5 and Rab11 are involved in the formation of early endocytosis,and Rab7 and Rab9 are involved in the formation of late endocytosis.Among them,Rab4 is mainly involved in the rapid filming process,and Rab11 is mainly involved.Slow filming,slow filming is regulated by a variety of proteins,so we mainly focus on Rab 11 for Rab kinase.Rab GTPase also relies on different effectors to help them work in different environments.The effector molecules of Rab11 include APPL,FIPs,AKAP10,MY05,EEA1 and etc.The NMDA receptor is an important glutamate receptor in the central nervous system and has an important influence on learning and memory.NMDA receptor abnormalities cause various types of neurodegenerative diseases.When we studied the mechanism of RIM1 involved in the regulation of NMDA receptor transport in mouse hippocampus,we found that four proteins interacted with both NMDA receptors and RIM1 proteins by mass spectrometry.We are interested in these four proteins,including FIP3.We tried to reveal the function of FIP3 in the nervous system by electrophysiological means.FIP3 knockdown has no effect on the basic transmission of synapses,but affects NMDA receptor-dependent LTP,but does not affect NMDA receptor-dependent LTD.To further investigate the function of FIP3 in synaptic plasticity,we found through biochemical tests that FIP3 is mainly distributed in hippocampus,is accumulated postsynapse,exists in NMDA receptor complex,but is not present in AMPA receptor complex.The results of co-immunoprecipitation showed that FIP3 did not directly bind to the NMDA receptor subunit.We further explored the functional mechanism of FIP3 involved in synaptic plasticity.Mass spectrometry found some interesting proteins,including CaMKⅡ,which revealed a direct interaction between FIP3 and CaMKⅡ through GST-pull down and co-immunoprecipitation,and this interaction was Calcium ion regulation,cell imaging revealed that knockdown of FIP3 caused translocation of CaMKⅡ,and co-localization with PSD95 was significantly increased.Therefore,we conclude that FIP3 may be involved in the regulation of CaMKⅡ function,which in turn affects synaptic plasticity.