Characterization of the interactions between inhibitor-1 and recombinant PP1 by NMR spectroscopy

Liang, Chu Ting; Lin, Yu Shan; Huang, Yi Choang; Huang, Hsien Lu; Yang, Jia Qian; Wu, Tsung Hsien; Chang, Chi‐Fon; Huang, Shing Jong; Huang, Hsien Bin; Lin, Ta Hsien

doi:10.1038/s41598-017-18383-x

Cited by 3 publications

(1 citation statement)

References 24 publications

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“…It is unclear if all PP1 holoenzymes are equally and proportionally inhibited by I-1*, or if the partial inhibition primarily affects a subset of holoenzymes. I-1-PP1 interaction involves the RVXF binding domain and is predicted to involve the PP1 acidic groove (Liang et al, 2018; Terrak et al, 2004). I-1* may therefore have higher binding affinity to PP1 holoenzymes in which the acidic groove is fully exposed, such as neurabin-PP1 (Ragusa et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

Foley

McKee

Ganguly

et al. 2023

Preprint

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Protein phosphatase 1 (PP1) regulates synaptic plasticity and has been described as a molecular constraint on learning and memory. There are three neuronal isoforms, PP1α, PP1β, and PP1γ, but little is known about their individual functions. PP1α and PP1γ are assumed to mediate the effects of PP1 on learning and memory based on their enrichment at dendritic spines and their preferential binding to neurabin and spinophilin, major PP1 synaptic scaffolding proteins. However, it was recently discovered that human de novo PP1β mutations cause intellectual disability, suggesting an important but ill-defined role for PP1β. In this study, we investigated the functions of each PP1 isoform in hippocampal synaptic physiology using conditional CA1-specific knockout mice. In stark contrast to classic PP1 function, we found that PP1β promotes synaptic plasticity as well as spatial memory. These changes in synaptic plasticity and memory are accompanied by changes in GluA1 phosphorylation, GluN2A levels, and dendritic spine density and morphology, including silent synapse number. These functions of PP1β reveal a previously unidentified signaling pathway regulating spine maturation and plasticity, broadening our understanding of the complex role of PP1 in synaptic physiology.

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Section: Discussionmentioning

confidence: 99%

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

Foley

McKee

Ganguly

et al. 2023

Preprint

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Microfluidics delivery of DARPP-32 into HeLa cells maintains viability for in-cell NMR spectroscopy

et al. 2022

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High-resolution structural studies of proteins and protein complexes in a native eukaryotic environment present a challenge to structural biology. In-cell NMR can characterize atomic resolution structures but requires high concentrations of labeled proteins in intact cells. Most exogenous delivery techniques are limited to specific cell types or are too destructive to preserve cellular physiology. The feasibility of microfluidics transfection or volume exchange for convective transfer, VECT, as a means to deliver labeled target proteins to HeLa cells for in-cell NMR experiments is demonstrated. VECT delivery does not require optimization or impede cell viability; cells are immediately available for long-term eukaryotic in-cell NMR experiments. In-cell NMR-based drug screening using VECT was demonstrated by collecting spectra of the sensor molecule DARPP32, in response to exogenous administration of Forskolin.

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Specificity determinants of phosphoprotein phosphatases controlling kinetochore functions

Garvanska

Nilsson

2020

Essays in Biochemistry

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Kinetochores are instrumental for accurate chromosome segregation by binding to microtubules in order to move chromosomes and by delaying anaphase onset through the spindle assembly checkpoint (SAC). Dynamic phosphorylation of kinetochore components is key to control these activities and is tightly regulated by temporal and spatial recruitment of kinases and phosphoprotein phosphatases (PPPs). Here we focus on PP1, PP2A-B56 and PP2A-B55, three PPPs that are important regulators of mitosis. Despite the fact that these PPPs share a very similar active site, they target unique ser/thr phosphorylation sites to control kinetochore function. Specificity is in part achieved by PPPs binding to short linear motifs (SLiMs) that guide their substrate specificity. SLiMs bind to conserved pockets on PPPs and are degenerate in nature, giving rise to a range of binding affinities. These SLiMs control the assembly of numerous substrate specifying complexes and their position and binding strength allow PPPs to target specific phosphorylation sites. In addition, the activity of PPPs is regulated by mitotic kinases and inhibitors, either directly at the activity level or through affecting PPP–SLiM interactions. Here, we discuss recent progress in understanding the regulation of PPP specificity and activity and how this controls kinetochore biology.

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Characterization of the interactions between inhibitor-1 and recombinant PP1 by NMR spectroscopy

Cited by 3 publications

References 24 publications

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

PP1β opposes classic PP1 function, inhibiting spine maturation and promoting LTP

Microfluidics delivery of DARPP-32 into HeLa cells maintains viability for in-cell NMR spectroscopy

Specificity determinants of phosphoprotein phosphatases controlling kinetochore functions

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