scholarly journals LKB1 and AMPK maintain epithelial cell polarity under energetic stress

2007 ◽  
Vol 177 (3) ◽  
pp. 387-392 ◽  
Author(s):  
Vincent Mirouse ◽  
Lance L. Swick ◽  
Nevzat Kazgan ◽  
Daniel St Johnston ◽  
Jay E. Brenman
Keyword(s):  
Tumor Suppressor ◽  
Cell Polarity ◽  
Growth Control ◽  
Epithelial Polarity ◽  
Energy Status ◽  
Ampk Signaling ◽  
Cellular Energy ◽  
Energetic Stress ◽  
Stress Dependent

LKB1 is mutated in both familial and spontaneous tumors, and acts as a master kinase that activates the PAR-1 polarity kinase and the adenosine 5′monophosphate–activated kinase (AMPK). This has led to the hypothesis that LKB1 acts as a tumor suppressor because it is required to maintain cell polarity and growth control through PAR-1 and AMPK, respectively. However, the genetic analysis of LKB1–AMPK signaling in vertebrates has been complicated by the existence of multiple redundant AMPK subunits. We describe the identification of mutations in the single Drosophila melanogaster AMPK catalytic subunit AMPKα. Surprisingly, ampkα mutant epithelial cells lose their polarity and overproliferate under energetic stress. LKB1 is required in vivo for AMPK activation, and lkb1 mutations cause similar energetic stress–dependent phenotypes to ampkα mutations. Furthermore, lkb1 phenotypes are rescued by a phosphomimetic version of AMPKα. Thus, LKB1 signals through AMPK to coordinate epithelial polarity and proliferation with cellular energy status, and this might underlie the tumor suppressor function of LKB1.

scholarly journals Synphilin-1 Interacts with AMPK and Increases AMPK Phosphorylation

2020 ◽  
Vol 21 (12) ◽  
pp. 4352 ◽  
Author(s):  
Tianxia Li ◽  
Jingnan Liu ◽  
Gongbo Guo ◽  
Bo Ning ◽  
Xueping Li ◽  
...  
Keyword(s):  
Energy Balance ◽  
Cultured Cells ◽  
Energy Status ◽  
Glutathione S Transferase ◽  
Cellular Functions ◽  
Ampk Signaling ◽  
Cellular Energy ◽  
Downstream Signaling ◽  
Compound C ◽  
Ampk Phosphorylation

A role for the cytoplasmic protein synphilin-1 in regulating energy balance has been demonstrated recently. Expression of synphilin-1 increases ATP levels in cultured cells. However, the mechanism by which synphilin-1 alters cellular energy status is unknown. Here, we used cell models and biochemical approaches to investigate the cellular functions of synphilin-1 on the AMP-activated protein kinase (AMPK) signaling pathway, which may affect energy balance. Overexpression of synphilin-1 increased AMPK phosphorylation (activation). Moreover, synphilin-1 interacted with AMPK by co-immunoprecipitation and GST (glutathione S-transferase) pull-down assays. Knockdown of synphilin-1 reduced AMPK phosphorylation. Overexpression of synphilin-1 also altered AMPK downstream signaling, i.e., a decrease in acetyl CoA carboxylase (ACC) phosphorylation, and an increase in p70S6K phosphorylation. Treatment of compound C (an AMPK inhibitor) reduced synphilin-1 binding with AMPK. In addition, compound C diminished synphilin-1-induced AMPK phosphorylation, and the increase in cellular ATP (adenosine triphosphate) levels. Our results demonstrated that synphilin-1 couples with AMPK, and they exert mutual effects on each other to regulate cellular energy status. These findings not only identify novel cellular actions of synphilin-1, but also provide new insights into the roles of synphilin-1 in regulating energy currency, ATP.

scholarly journals Intracellular ATP levels in mouse cortical excitatory neurons varies with sleep–wake states

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Akiyo Natsubori ◽  
Tomomi Tsunematsu ◽  
Akihiro Karashima ◽  
Hiromi Imamura ◽  
Naoya Kabe ◽  
...  
Keyword(s):  
Negative Energy ◽  
Simultaneous Increase ◽  
Energy Status ◽  
Cellular Energy ◽  
Intracellular Atp ◽  
Energy Demands ◽  
Atp Levels ◽  
Excitatory Neurons ◽  
The Brain

AbstractWhilst the brain is assumed to exert homeostatic functions to keep the cellular energy status constant under physiological conditions, this has not been experimentally proven. Here, we conducted in vivo optical recordings of intracellular concentration of adenosine 5’-triphosphate (ATP), the major cellular energy metabolite, using a genetically encoded sensor in the mouse brain. We demonstrate that intracellular ATP levels in cortical excitatory neurons fluctuate in a cortex-wide manner depending on the sleep-wake states, correlating with arousal. Interestingly, ATP levels profoundly decreased during rapid eye movement sleep, suggesting a negative energy balance in neurons despite a simultaneous increase in cerebral hemodynamics for energy supply. The reduction in intracellular ATP was also observed in response to local electrical stimulation for neuronal activation, whereas the hemodynamics were simultaneously enhanced. These observations indicate that cerebral energy metabolism may not always meet neuronal energy demands, consequently resulting in physiological fluctuations of intracellular ATP levels in neurons.

scholarly journals The tumor suppressor Lgl1 regulates NMII-A cellular distribution and focal adhesion morphology to optimize cell migration

2012 ◽  
Vol 23 (4) ◽  
pp. 591-601 ◽  
Author(s):  
Inbal Dahan ◽  
Ahuv Yearim ◽  
Yarin Touboul ◽  
Shoshana Ravid
Keyword(s):  
Tumor Suppressor ◽  
Cell Polarity ◽  
Focal Adhesion ◽  
Cellular Localization ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Membrane Dynamics ◽  
Migrating Cells

The Drosophila tumor suppressor Lethal (2) giant larvae (Lgl) regulates the apical–basal polarity in epithelia and asymmetric cell division. However, little is known about the role of Lgl in cell polarity in migrating cells. In this study we show direct physiological interactions between the mammalian homologue of Lgl (Lgl1) and the nonmuscle myosin II isoform A (NMII-A). We demonstrate that Lgl1 and NMII-A form a complex in vivo and provide data that Lgl1 inhibits NMII-A filament assembly in vitro. Furthermore, depletion of Lgl1 results in the unexpected presence of NMII-A in the cell leading edge, a region that is not usually occupied by this protein, suggesting that Lgl1 regulates the cellular localization of NMII-A. Finally, we show that depletion of Lgl1 affects the size and number of focal adhesions, as well as cell polarity, membrane dynamics, and the rate of migrating cells. Collectively these findings indicate that Lgl1 regulates the polarity of migrating cells by controlling the assembly state of NMII-A, its cellular localization, and focal adhesion assembly.

scholarly journals Chromophorylation of cyanobacteriochrome Slr1393 from Synechocystis sp. PCC 6803 is regulated by protein Slr2111 through allosteric interaction

2018 ◽  
Vol 293 (46) ◽  
pp. 17705-17715 ◽  
Author(s):  
Qi He ◽  
Qi-Ying Tang ◽  
Ya-Fang Sun ◽  
Ming Zhou ◽  
Wolfgang Gärtner ◽  
...  
Keyword(s):  
Visible Spectrum ◽  
Molar Ratio ◽  
Domain Pair ◽  
Energy Status ◽  
Cellular Energy ◽  
Cbs Domain ◽  
Cbs Domains ◽  
Pcc 6803

Cyanobacteriochromes (CBCRs) are photochromic proteins in cyanobacteria that act as photosensors. CBCRs bind bilins as chromophores and sense nearly the entire visible spectrum of light, but the regulation of the chromophorylation of CBCRs is unknown. Slr1393 from Synechocystis sp. PCC 6803 is a CBCR containing three consecutive GAF (cGMP phosphodiesterase, adenylyl cyclase, and FhlA protein) domains, of which only the third one (Slr1393g3) can be phycocyanobilin-chromophorylated. The protein Slr2111 from Synechocystis sp. PCC 6803 includes a cystathionine β-synthase (CBS) domain pair of an as yet unknown function at its N terminus. CBS domains are often characterized as sensors of cellular energy status by binding nucleotides. In this work, we demonstrate that Slr2111 strongly interacts with Slr1393 in vivo and in vitro, which generates a complex in a 1:1 molar ratio. This tight interaction inhibits the chromophorylation of Slr1393g3, even if the chromophore is present. Instead, the complex stability and thereby the chromophorylation of Slr1393 are regulated by the binding of nucleotides (ATP, ADP, AMP) to the CBS domains of Slr2111 with varying affinities. It is demonstrated that residues Asp-53 and Arg-97 of Slr2111 are involved in nucleotide binding. While ATP binds to Slr2111, the association between the two proteins gets weaker and chromophorylation of Slr1393 are enabled. In contrast, AMP binding to Slr2111 leads to a stronger association, thereby inhibiting the chromophorylation. It is concluded that Slr2111 acts as a sensor of the cellular energy status that regulates the chromophorylation of Slr1393 and thereby its function as a light-driven histidine kinase.

iTSP-PseAAC: Identify Tumor Suppressor Proteins by Using Fully Connected Neural Network and PseAAC

2021 ◽  
Vol 15 ◽  
Author(s):  
Muhammad Awais ◽  
Waqar Hussain ◽  
Nouman Rasool ◽  
Yaser Daanial Khan
Keyword(s):  
Tumor Suppressor ◽  
Cross Validation ◽  
Control Cell ◽  
Normal Function ◽  
In Vivo Studies ◽  
Tumor Suppressor Proteins ◽  
Proposed Model ◽  
Self Consistency

Background: The uncontrolled growth due to accumulation of genetic and epigenetic changes as a result of loss or reduction in the normal function of Tumor Suppressor Genes (TSGs) and Pro-oncogenes is known as cancer. TSGs control cell division and growth by repairing of DNA mistakes during replication and restrict the unwanted proliferation of a cell or activities, those are the part of tumor production. Objectives: This study aims to propose a novel, accurate, user-friendly model to predict tumor suppressor proteins, which would be freely available to experimental molecular biologists to assist them using in vitro and in vivo studies. Methods: The predictor model has used the input feature vector (IFV) calculated from the physicochemical properties of proteins based on FCNN to compute the accuracy, sensitivity, specificity, and MCC. The proposed model was validated against different exhaustive validation techniques i.e. self-consistency and cross-validation. Results: Using self-consistency, the accuracy is 99%, for cross-validation and independent testing has 99.80% and 100% accuracy respectively. The overall accuracy of the proposed model is 99%, sensitivity value 98% and specificity 99% and F1-score was 0.99. Conclusion: It concludes, the proposed model for prediction of the tumor suppressor proteins can predict the tumor suppressor proteins efficiently, but it still has space for improvements in computational ways as the protein sequences may rapidly increase, day by day.

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