scholarly journals Neuroprotective Function of 14-3-3 Proteins in Neurodegeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Tadayuki Shimada ◽  
Alyson E. Fournier ◽  
Kanato Yamagata
Keyword(s):  
Neurodegenerative Disease ◽  
Cellular Localization ◽  
Experimental Studies ◽  
Adaptor Proteins ◽  
Vast Number ◽  
Physiological Processes ◽  
Binding Partners ◽  
Neuroprotective Function ◽  
And Function ◽  
Regulation Of Enzyme Activity

14-3-3 proteins are abundantly expressed adaptor proteins that interact with a vast number of binding partners to regulate their cellular localization and function. They regulate substrate function in a number of ways including protection from dephosphorylation, regulation of enzyme activity, formation of ternary complexes and sequestration. The diversity of 14-3-3 interacting partners thus enables 14-3-3 proteins to impact a wide variety of cellular and physiological processes. 14-3-3 proteins are broadly expressed in the brain, and clinical and experimental studies have implicated 14-3-3 proteins in neurodegenerative disease. A recurring theme is that 14-3-3 proteins play important roles in pathogenesis through regulating the subcellular localization of target proteins. Here, we review the evidence that 14-3-3 proteins regulate aspects of neurodegenerative disease with a focus on their protective roles against neurodegeneration.

Matrix Metalloproteinases in Invertebrates

2020 ◽  
Vol 27 (11) ◽  
pp. 1068-1081
Author(s):  
Xi Liu ◽  
Dongwu Liu ◽  
Yangyang Shen ◽  
Mujie Huang ◽  
Lili Gao ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Immune Responses ◽  
Theoretical Basis ◽  
Regulatory Mechanism ◽  
Structure And Function ◽  
Catalytic Domains ◽  
Physiological Processes ◽  
Disease Occurrence ◽  
Complex Functions ◽  
And Function

Matrix Metalloproteinases (MMPs) belong to a family of metal-dependent endopeptidases which contain a series of conserved pro-peptide domains and catalytic domains. MMPs have been widely found in plants, animals, and microorganisms. MMPs are involved in regulating numerous physiological processes, pathological processes, and immune responses. In addition, MMPs play a key role in disease occurrence, including tumors, cardiovascular diseases, and other diseases. Compared with invertebrate MMPs, vertebrate MMPs have diverse subtypes and complex functions. Therefore, it is difficult to study the function of MMPs in vertebrates. However, it is relatively easy to study invertebrate MMPs because there are fewer subtypes of MMPs in invertebrates. In the present review, the structure and function of MMPs in invertebrates were summarized, which will provide a theoretical basis for investigating the regulatory mechanism of MMPs in invertebrates.

Mapping of Protein-Protein Interactions: Web-Based Resources for Revealing Interactomes

2019 ◽  
Vol 26 (21) ◽  
pp. 3890-3910 ◽  
Author(s):  
Branislava Gemovic ◽  
Neven Sumonja ◽  
Radoslav Davidovic ◽  
Vladimir Perovic ◽  
Nevena Veljkovic
Keyword(s):  
Drug Discovery ◽  
Protein Interactions ◽  
Protein Complexes ◽  
Experimental Studies ◽  
Protein Protein Interactions ◽  
Web Based ◽  
Prediction Tools ◽  
Physiological Processes ◽  
Modern Drug ◽  
Ppi Prediction

Background: The significant number of protein-protein interactions (PPIs) discovered by harnessing concomitant advances in the fields of sequencing, crystallography, spectrometry and two-hybrid screening suggests astonishing prospects for remodelling drug discovery. The PPI space which includes up to 650 000 entities is a remarkable reservoir of potential therapeutic targets for every human disease. In order to allow modern drug discovery programs to leverage this, we should be able to discern complete PPI maps associated with a specific disorder and corresponding normal physiology. Objective: Here, we will review community available computational programs for predicting PPIs and web-based resources for storing experimentally annotated interactions. Methods: We compared the capacities of prediction tools: iLoops, Struck2Net, HOMCOS, COTH, PrePPI, InterPreTS and PRISM to predict recently discovered protein interactions. Results: We described sequence-based and structure-based PPI prediction tools and addressed their peculiarities. Additionally, since the usefulness of prediction algorithms critically depends on the quality and quantity of the experimental data they are built on; we extensively discussed community resources for protein interactions. We focused on the active and recently updated primary and secondary PPI databases, repositories specialized to the subject or species, as well as databases that include both experimental and predicted PPIs. Conclusion: PPI complexes are the basis of important physiological processes and therefore, possible targets for cell-penetrating ligands. Reliable computational PPI predictions can speed up new target discoveries through prioritization of therapeutically relevant protein–protein complexes for experimental studies.

scholarly journals Understanding sex differences in long-term blood pressure regulation: insights from experimental studies and computational modeling

2019 ◽  
Vol 316 (5) ◽  
pp. H1113-H1123 ◽  
Author(s):  
Sameed Ahmed ◽  
Rui Hu ◽  
Jessica Leete ◽  
Anita T. Layton
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Computational Models ◽  
Experimental Studies ◽  
Pressure Control ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Physiological Processes ◽  
Key Players

Sex differences in blood pressure and the prevalence of hypertension are found in humans and animal models. Moreover, there has been a recent explosion of data concerning sex differences in nitric oxide, the renin-angiotensin-aldosterone system, inflammation, and kidney function. These data have the potential to reveal the mechanisms underlying male-female differences in blood pressure control. To elucidate the interactions among the multitude of physiological processes involved, one may apply computational models. In this review, we describe published computational models that represent key players in blood pressure regulation, and highlight sex-specific models and their findings.

scholarly journals The Link between VAPB Loss of Function and Amyotrophic Lateral Sclerosis

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1865
Author(s):  
Nica Borgese ◽  
Nicola Iacomino ◽  
Sara Francesca Colombo ◽  
Francesca Navone
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Adaptor Proteins ◽  
Loss Of Function ◽  
Membrane Contact Sites ◽  
Physiological Processes ◽  
Main Driver ◽  
Single Allele ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

The VAP proteins are integral adaptor proteins of the endoplasmic reticulum (ER) membrane that recruit a myriad of interacting partners to the ER surface. Through these interactions, the VAPs mediate a large number of processes, notably the generation of membrane contact sites between the ER and essentially all other cellular membranes. In 2004, it was discovered that a mutation (p.P56S) in the VAPB paralogue causes a rare form of dominantly inherited familial amyotrophic lateral sclerosis (ALS8). The mutant protein is aggregation-prone, non-functional and unstable, and its expression from a single allele appears to be insufficient to support toxic gain-of-function effects within motor neurons. Instead, loss-of-function of the single wild-type allele is required for pathological effects, and VAPB haploinsufficiency may be the main driver of the disease. In this article, we review the studies on the effects of VAPB deficit in cellular and animal models. Several basic cell physiological processes are affected by downregulation or complete depletion of VAPB, impinging on phosphoinositide homeostasis, Ca2+ signalling, ion transport, neurite extension, and ER stress. In the future, the distinction between the roles of the two VAP paralogues (A and B), as well as studies on motor neurons generated from induced pluripotent stem cells (iPSC) of ALS8 patients will further elucidate the pathogenic basis of p.P56S familial ALS, as well as of other more common forms of the disease.

scholarly journals Genome-wide identification and analysis of class III peroxidases in Betula pendula

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kewei Cai ◽  
Huixin Liu ◽  
Song Chen ◽  
Yi Liu ◽  
Xiyang Zhao ◽  
...  
Keyword(s):  
Stress Responses ◽  
Betula Pendula ◽  
Expression Patterns ◽  
Class Iii ◽  
Physiological Processes ◽  
Plant Life ◽  
Genome Wide ◽  
Plant Life Cycle ◽  
Class Iii Peroxidases ◽  
And Function

Abstract Background Class III peroxidases (POD) proteins are widely present in the plant kingdom that are involved in a broad range of physiological processes including stress responses and lignin polymerization throughout the plant life cycle. At present, POD genes have been studied in Arabidopsis, rice, poplar, maize and Chinese pear, but there are no reports on the identification and function of POD gene family in Betula pendula. Results We identified 90 nonredundant POD genes in Betula pendula. (designated BpPODs). According to phylogenetic relationships, these POD genes were classified into 12 groups. The BpPODs are distributed in different numbers on the 14 chromosomes, and some BpPODs were located sequentially in tandem on chromosomes. In addition, we analyzed the conserved domains of BpPOD proteins and found that they contain highly conserved motifs. We also investigated their expression patterns in different tissues, the results showed that some BpPODs might play an important role in xylem, leaf, root and flower. Furthermore, under low temperature conditions, some BpPODs showed different expression patterns at different times. Conclusions The research on the structure and function of the POD genes in Betula pendula plays a very important role in understanding the growth and development process and the molecular mechanism of stress resistance. These results lay the theoretical foundation for the genetic improvement of Betula pendula.

scholarly journals Roles of the novel coiled-coil protein Rng10 in septum formation during fission yeast cytokinesis

2016 ◽  
Vol 27 (16) ◽  
pp. 2528-2541 ◽  
Author(s):  
Yajun Liu ◽  
I-Ju Lee ◽  
Mingzhai Sun ◽  
Casey A. Lower ◽  
Kurt W. Runge ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Rho Gtpases ◽  
Cellular Localization ◽  
Affinity Purification ◽  
Coiled Coil ◽  
The Novel ◽  
Septum Formation ◽  
Division Site ◽  
And Function

Rho GAPs are important regulators of Rho GTPases, which are involved in various steps of cytokinesis and other processes. However, regulation of Rho-GAP cellular localization and function is not fully understood. Here we report the characterization of a novel coiled-coil protein Rng10 and its relationship with the Rho-GAP Rga7 in fission yeast. Both rng10Δ and rga7Δ result in defective septum and cell lysis during cytokinesis. Rng10 and Rga7 colocalize on the plasma membrane at the cell tips during interphase and at the division site during cell division. Rng10 physically interacts with Rga7 in affinity purification and coimmunoprecipitation. Of interest, Rga7 localization is nearly abolished without Rng10. Moreover, Rng10 and Rga7 work together to regulate the accumulation and dynamics of glucan synthases for successful septum formation in cytokinesis. Our results show that cellular localization and function of the Rho-GAP Rga7 are regulated by a novel protein, Rng10, during cytokinesis in fission yeast.

scholarly journals Centromere Protein B Null Mice are Mitotically and Meiotically Normal but Have Lower Body and Testis Weights

1998 ◽  
Vol 141 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Damien F. Hudson ◽  
Kerry J. Fowler ◽  
Elizabeth Earle ◽  
Richard Saffery ◽  
Paul Kalitsis ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Mammalian Species ◽  
Experimental Studies ◽  
Conflicting Evidence ◽  
Body Weights ◽  
Reduced Rate ◽  
And Function ◽  
Centromere Assembly ◽  
Mitosis And Meiosis

CENP-B is a constitutive centromere DNA-binding protein that is conserved in a number of mammalian species and in yeast. Despite this conservation, earlier cytological and indirect experimental studies have provided conflicting evidence concerning the role of this protein in mitosis. The requirement of this protein in meiosis has also not previously been described. To resolve these uncertainties, we used targeted disruption of the Cenpb gene in mouse to study the functional significance of this protein in mitosis and meiosis. Male and female Cenpb null mice have normal body weights at birth and at weaning, but these subsequently lag behind those of the heterozygous and wild-type animals. The weight and sperm content of the testes of Cenpb null mice are also significantly decreased. Otherwise, the animals appear developmentally and reproductively normal. Cytogenetic fluorescence-activated cell sorting and histological analyses of somatic and germline tissues revealed no abnormality. These results indicate that Cenpb is not essential for mitosis or meiosis, although the observed weight reduction raises the possibility that Cenpb deficiency may subtly affect some aspects of centromere assembly and function, and result in reduced rate of cell cycle progression, efficiency of microtubule capture, and/or chromosome movement. A model for a functional redundancy of this protein is presented.

scholarly journals cAMP-stimulated phosphorylation of diaphanous 1 regulates protein stability and interaction with binding partners in adrenocortical cells

2013 ◽  
Vol 24 (6) ◽  
pp. 848-857 ◽  
Author(s):  
Donghui Li ◽  
Eric B. Dammer ◽  
Natasha C. Lucki ◽  
Marion B. Sewer
Keyword(s):  
Oxysterol Binding Protein ◽  
Mitochondrial Movement ◽  
Binding Partners ◽  
Extracellular Signal ◽  
Camp Signaling Pathway ◽  
Integral Role ◽  
Mitochondrial Trafficking ◽  
The Stability ◽  
And Function ◽  
Β Tubulin

Diaphanous homologue 1 (DIAPH1) is a Rho effector protein that coordinates cellular dynamics by regulating microfilament and microtubule function. We previously showed that DIAPH1 plays an integral role in regulating the production of cortisol by controlling the rate of mitochondrial movement, by which activation of the adrenocorticotropin (ACTH)/cAMP signaling pathway stimulates mitochondrial trafficking and promotes the interaction between RhoA and DIAPH1. In the present study we use mass spectrometry to identify DIAPH1 binding partners and find that DIAPH1 interacts with several proteins, including RhoA, dynamin-1, kinesin, β-tubulin, β-actin, oxysterol-binding protein (OSBP)–related protein 2 (ORP2), and ORP10. Moreover, DIAPH1 is phosphorylated in response to dibutyryl cAMP (Bt2cAMP) at Thr-759 via a pathway that requires extracellular signal-related kinase (ERK). Alanine substitution of Thr-759 renders DIAPH1 more stable and attenuates the interaction between DIAPH1 and kinesin, ORP2, and actin but has no effect on the ability of the protein to interact with RhoA or β-tubulin. Finally, overexpression of a DIAPH1 T759A mutant significantly decreases the rate of Bt2cAMP-stimulated mitochondrial movement. Taken together, our findings establish a key role for phosphorylation in regulating the stability and function of DIAPH1.

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