Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain

Strack, Stefan; Kini, Sunil; Ebner, Ford F.; Wadzinski, Brian E.; Colbran, Roger J.

doi:10.1002/(sici)1096-9861(19991025)413:3<373::aid-cne2>3.0.co;2-z

Cited by 83 publications

(55 citation statements)

References 49 publications

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“…Additionally PP1, spinophilin, and CaMKII co-localize in dendritic spines of cultured neurons (Fig. 6 and [19]). Moreover, the association of PP1 and spinophilin with CaMKII in the striatum is strongly enhanced in parallel during maturation and aging.…”

Section: Discussionmentioning

confidence: 85%

“…We previously showed that PP1γ1 co-localizes with CaMKII in dendritic spines of cultured neurons [19]. In order to determine whether spinophilin co-localizes with CaMKII in dendritic spines, we immunostained cultured neurons for spinophilin and CaMKII.…”

Section: Resultsmentioning

confidence: 99%

“…Rat cortical cultures were prepared, stained, and imaged after 15 days in vitro as previously described [19].…”

Section: Methodsmentioning

confidence: 99%

“…One key regulator of CaMKII is protein phosphatase 1 (PP1) [13], a serine-threonine phosphatase that is also localized to dendritic spines and PSDs [18], [19]. Inhibition of PP1 enhances Thr286 autophosphorylation of CaMKIIα during the induction of long-term potentiation [20] and also increases synaptic strength in hippocampus of aged, but not young adult, animals [21].…”

Section: Introductionmentioning

confidence: 99%

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Age-Dependent Targeting of Protein Phosphatase 1 to Ca2+/Calmodulin-Dependent Protein Kinase II by Spinophilin in Mouse Striatum

2012

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Mechanisms underlying age-dependent changes of dendritic spines on striatal medium spiny neurons are poorly understood. Spinophilin is an F-actin- and protein phosphatase 1 (PP1)-binding protein that targets PP1 to multiple downstream effectors to modulate dendritic spine morphology and function. We found that calcium/calmodulin-dependent protein kinase II (CaMKII) directly and indirectly associates with N- and C-terminal domains of spinophilin, but F-actin can displace CaMKII from the N-terminal domain. Spinophilin co-localizes PP1 with CaMKII on the F-actin cytoskeleton in heterologous cells, and spinophilin co-localizes with synaptic CaMKII in neuronal cultures. Thr286 autophosphorylation enhances the binding of CaMKII to spinophilin in vitro and in vivo. Although there is no change in total levels of Thr286 autophosphorylation, maturation from postnatal day 21 into adulthood robustly enhances the levels of CaMKII that co-immunoprecipitate with spinophilin from mouse striatal extracts. Moreover, N- and C-terminal domain fragments of spinophilin bind more CaMKII from adult vs. postnatal day 21 striatal lysates. Total levels of other proteins that interact with C-terminal domains of spinophilin decrease during maturation, perhaps reducing competition for CaMKII binding to the C-terminal domain. In contrast, total levels of α-internexin and binding of α-internexin to the spinophilin N-terminal domain increases with maturation, perhaps bridging an indirect interaction with CaMKII. Moreover, there is an increase in the levels of myosin Va, α-internexin, spinophilin, and PP1 in striatal CaMKII immune complexes isolated from adult and aged mice compared to those from postnatal day 21. These changes in spinophilin/CaMKII interactomes may contribute to changes in striatal dendritic spine density, morphology, and function during normal postnatal maturation and aging.

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Section: Discussionmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

“…Rat cortical cultures were prepared, stained, and imaged after 15 days in vitro as previously described [19].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Age-Dependent Targeting of Protein Phosphatase 1 to Ca2+/Calmodulin-Dependent Protein Kinase II by Spinophilin in Mouse Striatum

2012

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“…Whether NR2C or NR2D subunits are localized presynaptically at cortical but not at thalamic afferents to LA will also need to be determined, as well as the molecular mechanisms downstream of PP2B/PP1 activation at both pathways. In the hippocampus, PP2B and PP1 have presynaptic and post-synaptic targets (Strack et al, 1999; Nakano-Kobayashi et al, 2007; Baumgärtel and Mansuy, 2012). In hippocampal and cortical neurons, PP1 can dephosphorylate NR2B (Farinelli et al, 2012; Prabhu Ramya et al, 2012), resulting in a downregulation of NMDAR activity (Farinelli et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Distinct molecular components for thalamic- and cortical-dependent plasticity in the lateral amygdala

Mirante¹,

Brandalise²,

Bohacek³

et al. 2014

Front. Mol. Neurosci.

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N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the lateral nucleus of the amygdala (LA) is a form of synaptic plasticity thought to be a cellular substrate for the extinction of fear memory. The LA receives converging inputs from the sensory thalamus and neocortex that are weakened following fear extinction. Combining field and patch-clamp electrophysiological recordings in mice, we show that paired-pulse low-frequency stimulation can induce a robust LTD at thalamic and cortical inputs to LA, and we identify different underlying molecular components at these pathways. We show that while LTD depends on NMDARs and activation of the protein phosphatases PP2B and PP1 at both pathways, it requires NR2B-containing NMDARs at the thalamic pathway, but NR2C/D-containing NMDARs at the cortical pathway. LTD appears to be induced post-synaptically at the thalamic input but presynaptically at the cortical input, since post-synaptic calcium chelation and NMDAR blockade prevent thalamic but not cortical LTD. These results highlight distinct molecular features of LTD in LA that may be relevant for traumatic memory and its erasure, and for pathologies such as post-traumatic stress disorder (PTSD).

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Phosphorylation of human tau protein by microtubule-associated kinases: GSK3? and cdk5 are key participants

et al. 2000

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Microtubules (MTs), primarily composed of α and β tubulin polymers, must often work in concert with microtubule‐associated proteins (MAPs) in order to modulate their functional demands. In a mature brain neuron, one of the key MAPs that resides primarily in the axonal compartment is the tau protein. Tau, in the adult human brain, is a set of six protein isoforms, whose binding affinity to MTs can be modulated by phosphorylation. In addition to the role that phosphorylation of tau plays in the “normal” physiology of neurons, hyperphosphorylated tau is the primary component of the fibrillary pathology in Alzheimer's disease (AD). Although many protein kinases are known to phosphorylate tau in vitro, the in vivo players contributing to the hyperphosphorylation of tau remain elusive. The experiments in this study attempt to define which protein kinases and protein phosphatases reside in the associated network of microtubules, thereby being strategically positioned to influence the phosphorylation of tau. Microtubule fractions are utilized to determine which of the microtubule‐associated kinases most readily impacts the phosphorylation of tau at “AD‐like” sites. Results from this study indicate that PKA, CK1, GSK3β, and cdk5 associate with microtubules. Among the MT‐associated kinases, GSK3β and cdk5 most readily contribute to the ATP‐induced “AD‐like” phosphorylation of tau. J. Neurosci. Res. 62:463–472, 2000. © 2000 Wiley‐Liss, Inc.

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Differential cellular and subcellular localization of protein phosphatase 1 isoforms in brain

Cited by 83 publications

References 49 publications

Age-Dependent Targeting of Protein Phosphatase 1 to Ca2+/Calmodulin-Dependent Protein Kinase II by Spinophilin in Mouse Striatum

Age-Dependent Targeting of Protein Phosphatase 1 to Ca2+/Calmodulin-Dependent Protein Kinase II by Spinophilin in Mouse Striatum

Distinct molecular components for thalamic- and cortical-dependent plasticity in the lateral amygdala

Phosphorylation of human tau protein by microtubule-associated kinases: GSK3? and cdk5 are key participants

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