Localization of phosphatase inhibitor-1 mRNA in the developing and adult rat brain in comparison with that of protein phosphatase-1 mRNAs

Sakagami, Hiroyuki; Ebina, Keiichi; Kondo, Hisatake

doi:10.1016/0169-328x(94)90273-9

Cited by 36 publications

(26 citation statements)

References 18 publications

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“…For example, inhibitor 1 (I1) is an ubiquitously expressed 28 kDa protein which upon phosphorylation by cAMP-dependent protein kinase A (PKA), results in potent inhibition of PP1. I1 messenger RNA (mRNA) is strongly expressed in the hippocampus [4] and I1 protein is found in the CA1 region of the hippocampus [5]. Other proteins such as G-substrate and dopamine and cAMP-regulated phosphoprotein Mr 32000 (DARPP-32), which exhibit considerable sequence overlap with I1, also inhibit PP1 [6].…”

Section: Endogenous Regulation Of Pp1 Activitymentioning

confidence: 99%

The role of protein phosphatase-1 in the modulation of synaptic and structural plasticity

MUNTON¹

2004

FEBS Letters

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Synaptic plasticity is a phenomenon contributing to changes in the efficacy of neuronal transmission. These changes are widely believed to be a major cellular basis for learning and memory. Protein phosphorylation is a key biochemical process involved in synaptic plasticity that operates through a tight balance between the action of protein kinases and protein phosphatases (PPs). Although the majority of research in this field has concentrated primarily on protein kinases, the significant role of PPs is becoming increasingly apparent. This review examines one such phosphatase, PP1, and highlights recent advances in the understanding of its intervention in synaptic and structural plasticity and the mechanisms of learning and memory.

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Section: Endogenous Regulation Of Pp1 Activitymentioning

confidence: 99%

The role of protein phosphatase-1 in the modulation of synaptic and structural plasticity

MUNTON¹

2004

FEBS Letters

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“…Error of change was calculated from standard errors of the mean using error propagation formulas. 6 as a Novel Cdk5 Site of Inhibitor-1-Inhibitor-1 was reported previously to be phosphorylated by Cdk5 at Ser 67 (13). Phosphopeptide maps of wild-type and S67A inhibitor-1 phosphorylated by the proline-directed serine/threonine kinases Cdk1, MAPK, and Cdk5 were generated during the characterization of this phosphorylation site (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Further investigation has revealed the presence of an additional Cdk5 site identified by mass spectrometry and confirmed by site-directed mutagenesis as Ser 6 . Basal levels of phospho-Ser 6 inhibitor-1, as detected by a phosphorylation state-specific antibody against the site, existed in specific regions of the brain and varied with age.…”

mentioning

confidence: 99%

“…Following discovery of the second site by phosphopeptide and phosphoamino acid analyses, mass spectrometric identification of the novel site as Ser 6 was confirmed by in vitro phosphorylation of site-directed mutants. Basal levels of phospho-Ser 6 inhibitor-1 as detected by a phosphorylation-state specific antibody generated against the site allowed demonstration of its relevance to in vivo systems.…”

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confidence: 99%

“…In the brain, inhibitor-1 can be found in many areas including the olfactory bulb, neostriatum, cerebral cortex, and the dentate gyrus of the hippocampus. The level of inhibitor-1 in the rest of the hippocampus is a matter of some debate; reports range from little or none to moderate amounts (2)(3)(4)(5)(6).…”

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Regulation of Protein Phosphatase Inhibitor-1 by Cyclin-dependent Kinase 5

Nguyen

Nishi

Kansy

et al. 2007

Journal of Biological Chemistry

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Inhibitor-1, the first identified endogenous inhibitor of protein phosphatase 1 (PP-1), was previously reported to be a substrate for cyclin-dependent kinase 5 (Cdk5) at Ser 67 . Further investigation has revealed the presence of an additional Cdk5 site identified by mass spectrometry and confirmed by site-directed mutagenesis as Ser 6 . Basal levels of phospho-Ser 6 inhibitor-1, as detected by a phosphorylation state-specific antibody against the site, existed in specific regions of the brain and varied with age. In the striatum, basal in vivo phosphorylation and dephosphorylation of Ser 6 were mediated by Cdk5, PP-2A, and PP-1, respectively. Additionally, calcineurin contributed to dephosphorylation under conditions of high Ca Phosphatases are now recognized as important players in processes ranging from muscle contraction to synaptic plasticity. Protein phosphatase inhibitor-1, or simply inhibitor-1 (I-1), 2 was identified from rabbit skeletal muscle in 1976 as an inhibitor of protein phosphatase 1 (PP-1) and a regulator of glycogen metabolism (1). In recent years, interest in the protein has focused on its role in heart failure and neuronal plasticity. In the brain, inhibitor-1 can be found in many areas including the olfactory bulb, neostriatum, cerebral cortex, and the dentate gyrus of the hippocampus. The level of inhibitor-1 in the rest of the hippocampus is a matter of some debate; reports range from little or none to moderate amounts (2-6).Inhibitor-1 is a heat-stable 19-kDa protein that possesses little ordered structure and a preponderance of glutamic acid and proline in its amino acid sequence (7). As a regulator of one of the three major serine/threonine phosphatases in mammalian cells that can itself be regulated by a major kinase, inhibitor-1 occupies an important position in neuronal signal transduction cascades. Only when phosphorylated by cAMP-dependent protein kinase (PKA) at Thr 35 does inhibitor-1 become a potent (IC 50 ϭ 1 nM) and selective inhibitor of PP-1 (1, 8, 9). Through its action on inhibitor-1, PKA can amplify cAMP signals by preventing the dephosphorylation of sites it shares with PP-1. That calcineurin (PP-2B, or Ca 2ϩ /calmodulin-dependent protein phosphatase) can inactivate I-1 by dephosphorylating the PKA site (10 -12) provides an added layer of complexity, as well as a point of integration for cAMP-and Ca 2ϩ -dependent second messenger systems. The ability of inhibitor-1 to link the actions of PKA and calcineurin to PP-1 has allowed it to occupy a central position in molecular models of synaptic plasticity.In 2001, inhibitor-1 was found to be phosphorylated at another residue (Ser 67 ) by cyclin-dependent kinase 5 (Cdk5) (13), a proline-directed serine/threonine kinase. This phosphorylation did not have an effect on the ability of phospho-Thr 35 inhibitor-1 to inhibit PP-1 and had only a mild effect on the ability of PKA to phosphorylate inhibitor-1 at Thr 35 . Despite its name, Cdk5 is not cyclin-dependent. Furthermore, unlike all other cyclin-dependent kinases, Cdk5 is mos...

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Interhemispheric connections between the infralimbic and entorhinal cortices: The endopiriform nucleus has limbic connections that parallel the sensory and motor connections of the claustrum

Watson

Smith

Alloway

2016

J of Comparative Neurology

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We have previously shown that the claustrum is part of an interhemispheric circuit that interconnects somesthetic-motor and visual-motor cortical regions. The role of the claustrum in processing limbic information, however, is poorly understood. Some evidence suggests that the dorsal endopiriform nucleus (DEn), which lies immediately ventral to the claustrum, has connections with limbic cortical areas and should be considered part of a claustrum-DEn complex. To determine whether DEn has similar patterns of cortical connections as the claustrum, we used anterograde and retrograde tracing techniques to elucidate the connectivity of DEn. Following injections of retrograde tracers into DEn, labeled neurons appeared bilaterally in the infralimbic (IL) cortex and ipsilaterally in the entorhinal and piriform cortices. Anterograde tracer injections in DEn revealed labeled terminals in the same cortical regions, but only in the ipsilateral hemisphere. These tracer injections also revealed extensive longitudinal projections throughout the rostrocaudal extent of the nucleus. Dual retrograde tracer injections into IL and lateral entorhinal cortex (LEnt) revealed intermingling of labeled neurons in ipsilateral DEn, including many double-labeled neurons. In other experiments, anterograde and retrograde tracers were separately injected into IL of each hemisphere of the same animal. This revealed an interhemispheric circuit in which IL projects bilaterally to DEn, with the densest terminal labeling appearing in the contralateral hemisphere around retrogradely-labeled neurons that project to IL in that hemisphere. By showing that DEn and claustrum have parallel sets of connections, these results suggest that DEn and claustrum perform similar functions in processing limbic and sensorimotor information, respectively.

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Localization of phosphatase inhibitor-1 mRNA in the developing and adult rat brain in comparison with that of protein phosphatase-1 mRNAs

Cited by 36 publications

References 18 publications

The role of protein phosphatase-1 in the modulation of synaptic and structural plasticity

The role of protein phosphatase-1 in the modulation of synaptic and structural plasticity

Regulation of Protein Phosphatase Inhibitor-1 by Cyclin-dependent Kinase 5

Interhemispheric connections between the infralimbic and entorhinal cortices: The endopiriform nucleus has limbic connections that parallel the sensory and motor connections of the claustrum

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