title: An essential role for inhibitor-2 regulation of protein phosphatase-1 in synaptic scaling.
abstract: Protein phosphatase-1 (PP1) activity is important for many calcium-dependent neuronal functions including Hebbian synaptic plasticity and learning and memory. PP1 activity is necessary for the induction of long-term depression, whereas downregulation of PP1 activity is required for the normal induction of long-term potentiation. However, how PP1 is activated is not clear. Moreover, it is not known whether PP1 plays a role in homeostatic synaptic scaling, another form of synaptic plasticity which functions to reset the neuronal firing rate in response to chronic neuronal activity perturbations. In this study, we found that PP1 inhibitor-2 (I-2) is phosphorylated at serine 43 (S43) in rat and mouse cortical neurons in response to bicuculine application. Expression of I-2 phosphorylation-blocking mutant I-2 (S43A) blocked the dephosphorylation of GluA2 at serine 880, AMPA receptor trafficking, and synaptic downscaling induced by bicuculline application. Our data suggest that the phosphorylation of I-2 at S43 appears to be mediated by L-type calcium channels and calcium/calmodulin-dependent myosin light-chain kinase. Our work thus reveals a novel calcium-induced PP1 activation pathway critical for homeostatic synaptic plasticity.
authors.affiliation: Neuroscience Center, Louisiana State University Health Science Center, New Orleans, Louisiana 70112, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Siddoway
authors.forename: Haider F
authors.initials: HF
authors.lastname: Altimimi
authors.forename: Hailong
authors.initials: H
authors.lastname: Hou
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.forename: David
authors.initials: D
authors.lastname: Stellwagen
authors.forename: Houhui
authors.initials: H
authors.lastname: Xia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020746:Calcium Channels, L-Type / Q000502:physiology; D002478:Cells, Cultured; D006706:Homeostasis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000201:enzymology / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D000097847:Protein Phosphatase Inhibitory Proteins
chemical_list: D020746:Calcium Channels, L-Type; D054645:Protein Phosphatase 1; D011506:Proteins; C024833:protein phosphatase inhibitor-2; D000097847:Protein Phosphatase Inhibitory Proteins