RT Journal Article
SR Electronic
T1 PP1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.10.480004
DO 10.1101/2022.02.10.480004
A1 Karl Foley
A1 Haider Altimimi
A1 Hailong Hou
A1 Yu Zhang
A1 Cody McKee
A1 Makaía M. Papasergi-Scott
A1 Hongtian Yang
A1 Abigail Mayer
A1 Nancy Ward
A1 David M. MacLean
A1 Angus C. Nairn
A1 David Stellwagen
A1 Houhui Xia
YR 2022
UL http://biorxiv.org/content/early/2022/02/24/2022.02.10.480004.abstract
AB Inhibitor-2 (I-2) is a prototypic inhibitor of protein phosphatase-1 (PP1), a major serine-threonine phosphatase that regulates synaptic plasticity and learning and memory. Although I-2 is a potent inhibitor of PP1 in vitro, our previous work has elucidated that, in vivo, I-2 may act as a positive regulator of PP1. Here we show that I-2 and PP1γ, but not PP1α, positively regulate synaptic transmission in hippocampal neurons. Moreover, we demonstrated that I-2 enhances PP1γ interaction with its major synaptic scaffold, neurabin, by Förster resonance energy transfer (FRET)/Fluorescence lifetime imaging microscopy (FLIM) studies, while having a limited effect on PP1 autoinhibitory phosphorylation. Furthermore, our study indicates that the effect of I-2 on PP1 activity in vivo is dictated by I-2 threonine-72 phosphorylation. Our work thus demonstrates a molecular mechanism by which I-2 positively regulates PP1 function in synaptic transmission.Competing Interest StatementThe authors have declared no competing interest.