1,895 results match your criteria coiled-coil signaling

Role of RhoA/ROCK signaling in Alzheimer's disease.

Behav Brain Res 2021 Jul 21;414:113481. Epub 2021 Jul 21.

Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, 400013, China; Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, China. Electronic address:

Rho-associated coiled-coil kinase (ROCK), a serine/threonine kinase regulated by the small GTPase RhoA, is involved in regulating cell migration, proliferation, and survival. Numerous studies have shown that the RhoA/ROCK signaling pathway can promote Alzheimer's disease (AD) occurrence. ROCK activation increases β-secretase activity and promotes amyloid-beta (Aβ) production; moreover, Aβ further activates ROCK. Read More

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Evolution of a σ-(c-di-GMP)-anti-σ switch.

Proc Natl Acad Sci U S A 2021 Jul;118(30)

Department of Molecular Microbiology, John Innes Centre, Norwich NR4 7UH, United Kingdom;

Filamentous actinobacteria of the genus have a complex lifecycle involving the differentiation of reproductive aerial hyphae into spores. We recently showed c-di-GMP controls this transition by arming a unique anti-σ, RsiG, to bind the sporulation-specific σ, WhiG. The RsiG-(c-di-GMP)-WhiG structure revealed that a monomeric RsiG binds c-di-GMP via two E(X)S(X)R(X)Q(X)D repeat motifs, one on each helix of an antiparallel coiled-coil. Read More

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Sensory cilia act as a specialized venue for regulated extracellular vesicle biogenesis and signaling.

Curr Biol 2021 Jul 8. Epub 2021 Jul 8.

Department of Genetics and Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ 08854, USA. Electronic address:

Ciliary extracellular vesicle (EV) shedding is evolutionarily conserved. In Chlamydomonas and C. elegans, ciliary EVs act as signaling devices. Read More

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Photoreaction of photoactivated adenylate cyclase from cyanobacterium Microcoleus chthonoplastes.

J Photochem Photobiol B 2021 Aug 6;221:112252. Epub 2021 Jul 6.

Department of Chemistry, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan. Electronic address:

The photochemical reaction of photoactivated adenylate cyclase from cyanobacterium Microcoleus chthonoplastes PCC 7420 (mPAC), which consists of a Per-Arnt-Sim (PAS), a light‑oxygene-voltage (LOV), and an adenylate cyclase (AC) domain, was investigated mainly using the time-resolved transient grating method. An absorption spectral change associated with an adduct formation between its chromophore (flavin mononucleotide) and a cysteine residue was observed with a time constant of 0.66 μs. Read More

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SlPHL1, a MYB-CC transcription factor identified from tomato, positively regulates the phosphate starvation response.

Physiol Plant 2021 Jul 15. Epub 2021 Jul 15.

Fujian Provincial Key Laboratory of Agroecological Processing and Safety Monitoring, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, People's Republic of China.

Inorganic phosphate (Pi) deficiency is a major limiting factor for plant growth and development. Previous reports have demonstrated that PHOSPHATE STARVATION RESPONSE 1 (PHR1) and OsPHR2 play central roles in Pi-starvation signaling in Arabidopsis and rice, respectively. However, the Pi-starvation signaling network in tomato (Solanum lycopersicum) is still not fully understood. Read More

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IGF-1 protects against angiotensin II-induced cardiac fibrosis by targeting αSMA.

Cell Death Dis 2021 Jul 9;12(7):688. Epub 2021 Jul 9.

Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.

The insulin-like growth factor 1 receptor (IGF-1R) signaling in cardiomyocytes is implicated in physiological hypertrophy and myocardial aging. Although fibroblasts account for a small amount of the heart, they are activated when the heart is damaged to promote cardiac remodeling. However, the role of IGF-1R signaling in cardiac fibroblasts is still unknown. Read More

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c-FLIP regulates autophagy by interacting with Beclin-1 and influencing its stability.

Cell Death Dis 2021 Jul 8;12(7):686. Epub 2021 Jul 8.

Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Sapienza University of Rome, Rome, Italy.

c-FLIP (cellular FLICE-like inhibitory protein) protein is mostly known as an apoptosis modulator. However, increasing data underline that c-FLIP plays multiple roles in cellular homoeostasis, influencing differently the same pathways depending on its expression level and isoform predominance. Few and controversial data are available regarding c-FLIP function in autophagy. Read More

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Effect of HSP90AB1 and CC domain interaction on Bcr-Abl protein cytoplasm localization and function in chronic myeloid leukemia cells.

Cell Commun Signal 2021 Jul 3;19(1):71. Epub 2021 Jul 3.

Department of Clinical Hematology, Key Laboratory of Laboratory Medical Diagnostics Designated By Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.

Background: The fusion oncoprotein Bcr-Abl is mostly located in the cytoplasm, which causes chronic myeloid leukemia (CML). After moving into the nucleus, the fusion protein can induce apoptosis of CML cells. The coiled-coil domain (CC domain) of Bcr-Abl protein plays a central role in the subcellular localization. Read More

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CCDC88A/GIV promotes HBV replication and progeny secretion via enhancing endosomal trafficking and blocking autophagic degradation.

Autophagy 2021 Jun 30:1-18. Epub 2021 Jun 30.

Institute of Biomedical Research, Hubei Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei province, China.

Hepatitis B virus (HBV) particles are thought to be secreted from hepatocytes through multivesicular bodies (MVBs); however, the cellular trafficking mechanisms prior to this process remain elusive. It has been reported that CCDC88A/GIV expression, which is involved in multiple aspects of vesicular trafficking, changes dynamically at different phases of chronic HBV infection. In this study, we focused on the role of CCDC88A/GIV in HBV replication. Read More

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The MLKL kinase-like domain dimerization is an indispensable step of mammalian MLKL activation in necroptosis signaling.

Cell Death Dis 2021 Jun 22;12(7):638. Epub 2021 Jun 22.

School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong, Shanghai, 201210, China.

MLKL phosphorylation by RIP3 is the commitment step of necroptosis execution, which could induce MLKL activation featured as MLKL monomer-oligomer transition. Here, we reported that the dimerization of the MLKL kinase-like domain was the direct consequence of RIP3 triggered MLKL-phosphorylation. Two inter-dimer interfaces were found in the crystal structure of human MLKL. Read More

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Inhibition of RhoA/Rho kinase signaling pathway by fasudil protects against kainic acid-induced neurite injury.

Brain Behav 2021 Jun 22. Epub 2021 Jun 22.

Department of Pharmacy, Zhejiang Hospital, Hangzhou, Zhejiang, China.

Aim: RhoA/Rho kinase pathway is essential for regulating cytoskeletal structure. Although its effect on normal neurite outgrowth has been demonstrated, the role of this pathway in seizure-induced neurite injury has not been revealed. The research examined the phosphorylation level of RhoA/Rho kinase signaling pathway and to clarify the effect of fasudil on RhoA/Rho kinase signaling pathway and neurite outgrowth in kainic acid (KA)-treated Neuro-2A cells and hippocampal neurons. Read More

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Screening and identification of Theileria annulata subtelomere-encoded variable secreted protein-950454 (SVSP454) interacting proteins from bovine B cells.

Parasit Vectors 2021 Jun 11;14(1):319. Epub 2021 Jun 11.

State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Science, Xujiaping 1, Lanzhou, Gansu, 730046, People's Republic of China.

Background: Theileria annulata is a protozoan parasite that can infect and transform bovine B cells, macrophages, and dendritic cells. The mechanism of the transformation is still not well understood, and some parasite molecules have been identified, which contribute to cell proliferation by regulating host signaling pathways. Subtelomeric variable secreted proteins (SVSPs) of Theileria might affect the host cell phenotype, but its function is still not clear. Read More

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The PHY Domain Dimer Interface of Bacteriophytochromes Mediates Cross-talk between Photosensory Modules and Output Domains.

J Mol Biol 2021 Jul 9;433(15):167092. Epub 2021 Jun 9.

Institute of Biochemistry, Graz University of Technology, 8010 Graz, Austria; BioTechMed-Graz, 8010 Graz, Austria. Electronic address:

Protein dynamics play a major role for the catalytic function of enzymes, the interaction of protein complexes or signal integration in regulatory proteins. In the context of multi-domain proteins involved in light-regulation of enzymatic effectors, the central role of conformational dynamics is well established. Light activation of sensory modules is followed by long-range signal transduction to different effectors; rather than domino-style structural rearrangements, a complex interplay of functional elements is required to maintain functionality. Read More

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Sequences in the stalk domain regulate auto-inhibition and ciliary tip localization of the immotile kinesin-4 KIF7.

J Cell Sci 2021 Jul 8;134(13). Epub 2021 Jul 8.

Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

The kinesin-4 member KIF7 plays critical roles in Hedgehog signaling in vertebrate cells. KIF7 is an atypical kinesin as it binds to microtubules but is immotile. We demonstrate that, like conventional kinesins, KIF7 is regulated by auto-inhibition, as the full-length protein is inactive for microtubule binding in cells. Read More

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Cell adhesion factors in the orbitofrontal cortex control cue-induced reinstatement of cocaine seeking and amygdala-dependent goal seeking.

J Neurosci 2021 May 27. Epub 2021 May 27.

Departments of Pediatrics and Psychiatry, Emory University School of Medicine, United States

Repeated cocaine exposure causes dendritic spine loss in the orbitofrontal cortex, which might contribute to poor orbitofrontal cortical function following drug exposure. One challenge, however, has been verifying links between neuronal structural plasticity and behavior, if any. Here we report that cocaine self-administration triggers the loss of dendritic spines on excitatory neurons in the orbitofrontal cortex of male and female mice (as has been reported in rats). Read More

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Kallikrein-11, in Association with Coiled-Coil Domain Containing 25, as a Potential Prognostic Marker for Cholangiocarcinoma with Lymph Node Metastasis.

Molecules 2021 May 22;26(11). Epub 2021 May 22.

Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, KhonKaen University, Khon Kaen 40002, Thailand.

Cholangiocarcinoma (CCA) is a malignancy arising from cholangiocytes. Currently, the treatment and prognosis for CCA are mostly poor. Recently, we have reported that coiled-coil domain containing 25 (CCDC25) protein level in the sera may be a diagnostic marker for CCA. Read More

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Genetic Risk and Phenotype Correlation of Primary Open-Angle Glaucoma Based on Rho-Kinase Gene Polymorphisms.

J Clin Med 2021 May 1;10(9). Epub 2021 May 1.

Department of Ophthalmology, Seoul National University Hospital, Seoul 03080, Korea.

Rho-associated coiled-coil kinase (ROCK) signaling can affect glaucoma risk by regulating trabecular meshwork outflow. We investigated the effect of gene polymorphism on the risks of primary open-angle glaucoma (POAG) and POAG-related phenotypes including intraocular pressure (IOP) in a Korean population. A total of 24 single-nucleotide polymorphisms (SNPs) from and were selected and genotyped for 363 POAG patients and 213 healthy controls. Read More

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Grouper TRAF5 exerts negative regulation on antiviral immune response against iridovirus.

Fish Shellfish Immunol 2021 Aug 29;115:7-13. Epub 2021 May 29.

Guangdong Laboratory for Lingnan Modern Agriculture, Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, PR China. Electronic address:

Tumor necrosis factor receptor-associated factor 5 (TRAF5) is an intracellular protein that binds to the cytoplasmic portion of tumor necrosis factor receptors and mediates the activation of downstream nuclear factor-kappa B (NF-κB), interferon regulatory factor 3, and mitogen activated protein kinase signaling pathways. Compared with other TRAF proteins, TRAF5 is largely unknown in teleosts. In the present study, a TRAF5 homologue (HgTRAF5) from the hybrid grouper (Epinephelus fuscoguttatus♂ × Epinephelus lanceolatus♀) was cloned and characterized. Read More

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Transcription- and phosphorylation-dependent control of a functional interplay between XBP1s and PINK1 governs mitophagy and potentially impacts Parkinson disease pathophysiology.

Autophagy 2021 May 24:1-23. Epub 2021 May 24.

INSERM, CNRS, IPMC, Team Labeled "Laboratory of Excellence (LABEX) Distalz", Sophia-Antipolis, Université Côte d'Azur, Valbonne, France.

Parkinson disease (PD)-affected brains show consistent endoplasmic reticulum (ER) stress and mitophagic dysfunctions. The mechanisms underlying these perturbations and how they are directly linked remain a matter of questions. XBP1 is a transcription factor activated upon ER stress after unconventional splicing by the nuclease ERN1/IREα thereby yielding XBP1s, whereas PINK1 is a kinase considered as the sensor of mitochondrial physiology and a master gatekeeper of mitophagy process. Read More

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The TIR-NBS protein TN13 associates with the CC-NBS-LRR resistance protein RPS5 and contributes to RPS5-triggered immunity in Arabidopsis.

Plant J 2021 May 13. Epub 2021 May 13.

State Key Laboratory of Ecological Control of Fujian-Taiwan Crop Pests, Key Laboratory of Ministry of Education for Genetics, Breeding and Multiple Utilization of Crops, Plant Immunity Center, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

Nucleotide-binding site (NBS)-leucine-rich repeat (LRR) domain receptor (NLR) proteins play important roles in plant innate immunity by recognizing pathogen effectors. The Toll/interleukin-1 receptor (TIR)-NBS (TN) proteins belong to a subtype of the atypical NLRs, but their function in plant immunity is poorly understood. The well-characterized Arabidopsis thaliana typical coiled-coil (CC)-NBS-LRR (CNL) protein Resistance to Pseudomonas syringae 5 (RPS5) is activated after recognizing the Pseudomonas syringae type III effector AvrPphB. Read More

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TSC1 binding to lysosomal PIPs is required for TSC complex translocation and mTORC1 regulation.

Mol Cell 2021 07 10;81(13):2705-2721.e8. Epub 2021 May 10.

University of Münster, Institute of Biochemistry, 48149 Münster, Germany; University of Osnabrück, Department of Biology/Chemistry, Structural Biology Section, 49076 Osnabrück, Germany. Electronic address:

The TSC complex is a critical negative regulator of the small GTPase Rheb and mTORC1 in cellular stress signaling. The TSC2 subunit contains a catalytic GTPase activating protein domain and interacts with multiple regulators, while the precise function of TSC1 is unknown. Here we provide a structural characterization of TSC1 and define three domains: a C-terminal coiled-coil that interacts with TSC2, a central helical domain that mediates TSC1 oligomerization, and an N-terminal HEAT repeat domain that interacts with membrane phosphatidylinositol phosphates (PIPs). Read More

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The Integrin Signaling Network Promotes Axon Regeneration via the Src-Ephexin-RhoA GTPase Signaling Axis.

J Neurosci 2021 Jun 7;41(22):4754-4767. Epub 2021 May 7.

Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan

Axon regeneration is an evolutionarily conserved process essential for restoring the function of damaged neurons. In hermaphrodites, initiation of axon regeneration is regulated by the RhoA GTPase-ROCK (Rho-associated coiled-coil kinase)-regulatory nonmuscle myosin light-chain phosphorylation signaling pathway. However, the upstream mechanism that activates the RhoA pathway remains unknown. Read More

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Regulation of Cell Death and Signaling by Pore-Forming Resistosomes.

Annu Rev Phytopathol 2021 May 6. Epub 2021 May 6.

State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing 100101, China; email:

Nucleotide-binding leucine-rich repeat receptors (NLRs) are the largest class of immune receptors in plants. They play a key role in the plant surveillance system by monitoring pathogen effectors that are delivered into the plant cell. Recent structural biology and biochemical analyses have uncovered how NLRs are activated to form oligomeric resistosomes upon the recognition of pathogen effectors. Read More

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Coiled-Coil Domain-Containing (CCDC) Proteins: Functional Roles in General and Male Reproductive Physiology.

Reprod Sci 2021 May 3. Epub 2021 May 3.

Department of Animal Biology, University of Hyderabad, Hyderabad, 500046, India.

The coiled-coil domain-containing (CCDC) proteins have been implicated in a variety of physiological and pathological processes. Their functional roles vary from their interaction with molecular components of signaling pathways to determining the physiological functions at the cellular and organ level. Thus, they govern important functions like gametogenesis, embryonic development, hematopoiesis, angiogenesis, and ciliary development. Read More

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Physical tuning of galectin-3 signaling.

Proc Natl Acad Sci U S A 2021 May;118(19)

J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611

Galectin-3 (Gal3) exhibits dynamic oligomerization and promiscuous binding, which can lead to concomitant activation of synergistic, antagonistic, or noncooperative signaling pathways that alter cell behavior. Conferring signaling pathway selectivity through mutations in the Gal3-glycan binding interface is challenged by the abundance of common carbohydrate types found on many membrane glycoproteins. Here, employing alpha-helical coiled-coils as scaffolds to create synthetic Gal3 constructs with defined valency, we demonstrate that oligomerization can physically regulate extracellular signaling activity of Gal3. Read More

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The Cellular Prion Protein-ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases.

Front Cell Neurosci 2021 12;15:660683. Epub 2021 Apr 12.

Inserm UMR 942, Hôpital Lariboisière, Paris, France.

Amyloid-based neurodegenerative diseases such as prion, Alzheimer's, and Parkinson's diseases have distinct etiologies and clinical manifestations, but they share common pathological events. These diseases are caused by abnormally folded proteins (pathogenic prions PrP in prion diseases, β-amyloids/Aβ and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease) that display β-sheet-enriched structures, propagate and accumulate in the nervous central system, and trigger neuronal death. In prion diseases, PrP-induced corruption of the physiological functions exerted by normal cellular prion proteins (PrP) present at the cell surface of neurons is at the root of neuronal death. Read More

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How autophagy controls the intestinal epithelial barrier.

Autophagy 2021 Apr 27:1-18. Epub 2021 Apr 27.

Department of Immunology, University of Toronto, Toronto, Canada.

Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal epithelium is of particular interest, as several autophagy-related genes have been associated with intestinal disease. Autophagy and its regulatory mechanisms are involved in both homeostasis and repair of the intestine, supporting intestinal barrier function in response to cellular stress through tight junction regulation and protection from cell death. Read More

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Mechanistic dissection of spatial organization in NF-κB signaling pathways by hybrid simulations.

Integr Biol (Camb) 2021 May;13(5):109-120

Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA.

The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is one of the most important transcription factors involved in the regulation of inflammatory signaling pathways. Inappropriate activation of these pathways has been linked to autoimmunity and cancers. Emerging experimental evidences have been showing the existence of elaborate spatial organizations for various molecular components in the pathways. Read More

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Dimer Asymmetry and Light Activation Mechanism in Blue-Light Sensor Histidine Kinase.

mBio 2021 04 20;12(2). Epub 2021 Apr 20.

Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires, Argentina

The ability to sense and respond to environmental cues is essential for adaptation and survival in living organisms. In bacteria, this process is accomplished by multidomain sensor histidine kinases that undergo autophosphorylation in response to specific stimuli, thereby triggering downstream signaling cascades. However, the molecular mechanism of allosteric activation is not fully understood in these important sensor proteins. Read More

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ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease.

J Clin Oncol 2021 Jun 20;39(17):1888-1898. Epub 2021 Apr 20.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: The rho-associated coiled-coil-containing protein kinase-2 (ROCK2) signaling pathway regulates the Th17/regulatory T cells balance and controls profibrotic pathways. Selective ROCK2 inhibition with belumosudil (KD025) may offer a novel approach to the management of chronic graft-versus-host disease (cGVHD).

Patients And Methods: A phase IIa, open-label, dose-finding study of belumosudil enrolled 54 patients with cGVHD who had received one to three prior lines of therapy (LOTs). Read More

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