scholarly journals Critical Functions of PP2A-Like Protein Phosphotases in Regulating Meiotic Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Wen-Long Lei ◽  
Wei-Ping Qian ◽  
Qing-Yuan Sun
Keyword(s):  
Birth Defects ◽  
Protein Phosphatase ◽  
Dynamic Equilibrium ◽  
Protein Phosphatases ◽  
Meiotic Cell ◽  
Single Cycle ◽  
Post Translational Modifications ◽  
Meiotic Progression ◽  
Protein Dephosphorylation

Meiosis is essential to the continuity of life in sexually-reproducing organisms through the formation of haploid gametes. Unlike somatic cells, the germ cells undergo two successive rounds of meiotic divisions after a single cycle of DNA replication, resulting in the decrease in ploidy. In humans, errors in meiotic progression can cause infertility and birth defects. Post-translational modifications, such as phosphorylation, ubiquitylation and sumoylation have emerged as important regulatory events in meiosis. There are dynamic equilibrium of protein phosphorylation and protein dephosphorylation in meiotic cell cycle process, regulated by a conservative series of protein kinases and protein phosphatases. Among these protein phosphatases, PP2A, PP4, and PP6 constitute the PP2A-like subfamily within the serine/threonine protein phosphatase family. Herein, we review recent discoveries and explore the role of PP2A-like protein phosphatases during meiotic progression.

scholarly journals CDK Regulation of Meiosis: Lessons from S. cerevisiae and S. pombe

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 723
Author(s):  
Anne M. MacKenzie ◽  
Soni Lacefield
Keyword(s):  
Fission Yeast ◽  
Yeast Species ◽  
Regulatory System ◽  
Cyclin Dependent Kinase ◽  
Post Translational Modifications ◽  
Regulatory Subunits ◽  
Meiotic Progression ◽  
The Past ◽  
Cdk Regulation

Meiotic progression requires precise orchestration, such that one round of DNA replication is followed by two meiotic divisions. The order and timing of meiotic events is controlled through the modulation of the phosphorylation state of proteins. Key components of this phospho-regulatory system include cyclin-dependent kinase (CDK) and its cyclin regulatory subunits. Over the past two decades, studies in budding and fission yeast have greatly informed our understanding of the role of CDK in meiotic regulation. In this review, we provide an overview of how CDK controls meiotic events in both budding and fission yeast. We discuss mechanisms of CDK regulation through post-translational modifications and changes in the levels of cyclins. Finally, we highlight the similarities and differences in CDK regulation between the two yeast species. Since CDK and many meiotic regulators are highly conserved, the findings in budding and fission yeasts have revealed conserved mechanisms of meiotic regulation among eukaryotes.

Role of protein phosphatases in the activation of CFTR (ABCC7) by genistein and bromotetramisole

2000 ◽  
Vol 279 (1) ◽  
pp. C108-C119 ◽  
Author(s):  
Jiexin Luo ◽  
Tang Zhu ◽  
Alexandra Evagelidis ◽  
Mary D. Pato ◽  
John W. Hanrahan
Keyword(s):  
Protein Phosphatase ◽  
Chloride Channels ◽  
Protein Phosphatases ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Airway Epithelial Cells ◽  
Transmembrane Conductance Regulator ◽  
Airway Epithelial ◽  
Ovary Cells

Genistein and bromotetramisole (Br-t) strongly activate cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) chloride channels on Chinese hamster ovary cells and human airway epithelial cells. We have examined the possible role of phosphatases in stimulation by these drugs using patch-clamp and biochemical methods. Genistein inhibited the spontaneous rundown of channel activity that occurs after membrane patches are excised from cAMP-stimulated cells but had no effect on purified protein phosphatase type 1 (PP1), PP2A, PP2B, PP2C, or endogenous phosphatases when assayed as [32P]PO4release from prelabeled casein, recombinant GST-R domain fusion protein, or immunoprecipitated full-length CFTR. Br-t also slowed rundown of CFTR channels, but, in marked contrast to genistein, it did inhibit all four protein phosphatases tested. Half-maximal inhibition of PP2A and PP2C was observed with 0.5 and 1.5 mM Br-t, respectively. Protein phosphatases were also sensitive to (+)- p-Br-t, a stereoisomer of Br-t that does not inhibit alkaline phosphatases. Br-t appeared to act exclusively through phosphatases since it did not affect CFTR channels in patches that had low apparent endogenous phosphatase activity (i.e., those lacking spontaneous rundown). We conclude that genistein and Br-t act through different mechanisms. Genistein stimulates CFTR without inhibiting phosphatases, whereas Br-t acts by inhibiting a membrane-associated protein phosphatase (probably PP2C) that presumably allows basal phosphorylation to accumulate.

Role of protein phosphatases in the run down of guinea pig cardiac Cav1.2 Ca2+ channels

2016 ◽  
Vol 310 (10) ◽  
pp. C773-C779 ◽  
Author(s):  
Lifeng Yu ◽  
Jianjun Xu ◽  
Etsuko Minobe ◽  
Asako Kameyama ◽  
Lei Yang ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Protein Phosphatase ◽  
Ventricular Myocytes ◽  
Protein Phosphatases ◽  
Slow Phase ◽  
Patch Clamp Technique ◽  
Time Constants ◽  
Open Time ◽  
Protein Phosphatase Type

This study aimed to investigate protein phosphatases involved in the run down of Cav1.2 Ca2+ channels. Single ventricular myocytes obtained from adult guinea pig hearts were used to record Ca2+ channel currents with the patch-clamp technique. Calmodulin (CaM) and ATP were used to restore channel activity in inside-out patches. Inhibitors of protein phosphatases were applied to investigate the role of phosphatases. The specific protein phosphatase type 1 (PP1) inhibitor (PP1 inhibitor-2) and protein phosphatase type 2A (PP2A) inhibitor (fostriecin) abolished the slow run down of Cav1.2 Ca2+ channels, which was evident as the time-dependent attenuation of the reversing effect of CaM/ATP on the run down. However, protein phosphatase type 2B (PP2B, calcineurin) inhibitor cyclosporine A together with cyclophilin A had no effect on the channel run down. Furthermore, PP1 inhibitor-2 mainly prolonged the open time constants of the channel, specifically, the slow open time. Fostriecin primarily shortened the slow close time constants. Our data suggest that PP1 and PP2A were involved in the slow phase of Cav1.2 Ca2+ channel run down. In addition, they exerted different effects on the open-close kinetics of the channel. All above support the view that PP1 and PP2A may dephosphorylate distinct phosphorylation sites on the Cav1.2 Ca2+ channel.

scholarly journals Protein phosphatases at the nuclear envelope

2018 ◽  
Vol 46 (1) ◽  
pp. 173-182 ◽  
Author(s):  
Raquel Sales Gil ◽  
Ines J. de Castro ◽  
Jerusalem Berihun ◽  
Paola Vagnarelli
Keyword(s):  
Nuclear Envelope ◽  
Lipid Membranes ◽  
Protein Phosphatases ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Post Translational Modifications ◽  
Cellular Machinery ◽  
Pore Complexes ◽  
Cellular Compartments

The nuclear envelope (NE) is a unique topological structure formed by lipid membranes (Inner and Outer Membrane: IM and OM) interrupted by open channels (Nuclear Pore complexes). Besides its well-established structural role in providing a physical separation between the genome and the cytoplasm and regulating the exchanges between the two cellular compartments, it has become quite evident in recent years that the NE also represents a hub for localized signal transduction. Mechanical, stress, or mitogen signals reach the nucleus and trigger the activation of several pathways, many effectors of which are processed at the NE. Therefore, the concept of the NE acting just as a barrier needs to be expanded to embrace all the dynamic processes that are indeed associated with it. In this context, dynamic protein association and turnover coupled to reversible post-translational modifications of NE components can provide important clues on how this integrated cellular machinery functions as a whole. Reversible protein phosphorylation is the most used mechanism to control protein dynamics and association in cells. Keys to the reversibility of the system are protein phosphatases and the regulation of their activity in space and time. As the NE is clearly becoming an interesting compartment for the control and transduction of several signalling pathways, in this review we will focus on the role of Protein Phosphatases at the NE since the significance of this class of proteins in this context has been little explored.

Differential role of four cysteines on the activity of a low M r phosphotyrosine protein phosphatase

FEBS Letters ◽  
1992 ◽  
Vol 310 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Paola Chiarugi ◽  
Riccardo Marzocchini ◽  
Giovanni Raugei ◽  
Claudia Pazzagli ◽  
Andrea Berti ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Phosphotyrosine Protein Phosphatase

Saccharomyces cerevisiae Checkpoint Genes MEC1, RAD17 and RAD24 Are Required for Normal Meiotic Recombination Partner Choice

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 607-620 ◽  
Author(s):  
Jeremy M Grushcow ◽  
Teresa M Holzen ◽  
Ken J Park ◽  
Ted Weinert ◽  
Michael Lichten ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Mitotic Checkpoint ◽  
Partner Choice ◽  
Wild Type ◽  
Spore Viability ◽  
Checkpoint Signaling ◽  
Ectopic Recombination ◽  
Meiotic Progression ◽  
Checkpoint Genes

Abstract Checkpoint gene function prevents meiotic progression when recombination is blocked by mutations in the recA homologue DMC1. Bypass of dmc1 arrest by mutation of the DNA damage checkpoint genes MEC1, RAD17, or RAD24 results in a dramatic loss of spore viability, suggesting that these genes play an important role in monitoring the progression of recombination. We show here that the role of mitotic checkpoint genes in meiosis is not limited to maintaining arrest in abnormal meioses; mec1-1, rad24, and rad17 single mutants have additional meiotic defects. All three mutants display Zip1 polycomplexes in two- to threefold more nuclei than observed in wild-type controls, suggesting that synapsis may be aberrant. Additionally, all three mutants exhibit elevated levels of ectopic recombination in a novel physical assay. rad17 mutants also alter the fraction of recombination events that are accompanied by an exchange of flanking markers. Crossovers are associated with up to 90% of recombination events for one pair of alleles in rad17, as compared with 65% in wild type. Meiotic progression is not required to allow ectopic recombination in rad17 mutants, as it still occurs at elevated levels in ndt80 mutants that arrest in prophase regardless of checkpoint signaling. These observations support the suggestion that MEC1, RAD17, and RAD24, in addition to their proposed monitoring function, act to promote normal meiotic recombination.

scholarly journals System-wide identification and prioritization of enzyme substrates by thermal analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Amir Ata Saei ◽  
Christian M. Beusch ◽  
Pierre Sabatier ◽  
Juan Astorga Wells ◽  
Hassan Gharibi ◽  
...  
Keyword(s):  
Thermal Analysis ◽  
Thioredoxin Reductase ◽  
Structural Level ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Enzyme Substrate ◽  
Thioredoxin Reductase 1 ◽  
Enzyme Substrates ◽  
Substrate Proteins

AbstractDespite the immense importance of enzyme–substrate reactions, there is a lack of general and unbiased tools for identifying and prioritizing substrate proteins that are modified by the enzyme on the structural level. Here we describe a high-throughput unbiased proteomics method called System-wide Identification and prioritization of Enzyme Substrates by Thermal Analysis (SIESTA). The approach assumes that the enzymatic post-translational modification of substrate proteins is likely to change their thermal stability. In our proof-of-concept studies, SIESTA successfully identifies several known and novel substrate candidates for selenoprotein thioredoxin reductase 1, protein kinase B (AKT1) and poly-(ADP-ribose) polymerase-10 systems. Wider application of SIESTA can enhance our understanding of the role of enzymes in homeostasis and disease, opening opportunities to investigate the effect of post-translational modifications on signal transduction and facilitate drug discovery.

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