scholarly journals Store-Operated Calcium Channels

2015 ◽  
Vol 95 (4) ◽  
pp. 1383-1436 ◽  
Author(s):  
Murali Prakriya ◽  
Richard S. Lewis
Keyword(s):  
Calcium Channels ◽  
Molecular Mechanisms ◽  
Major Pathway ◽  
Surface Receptors ◽  
Store Operate Calcium Entry ◽  
Channel Properties ◽  
Structural Insights ◽  
Unique Mechanism ◽  
Stimulation Of

Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca2+ sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca2+ from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca2+ depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease.

scholarly journals Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Pietro Poggio ◽  
Matteo Sorge ◽  
Laura Seclì ◽  
Mara Brancaccio
Keyword(s):  
Tumor Microenvironment ◽  
Cell Surface ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Diagnostic Tools ◽  
Surface Receptors ◽  
And Behavior ◽  
Cancer Cell Signaling ◽  
The Impact ◽  
Stimulation Of

HSP90 is released by cancer cells in the tumor microenvironment where it associates with different co-chaperones generating complexes with specific functions, ranging from folding and activation of extracellular clients to the stimulation of cell surface receptors. Emerging data indicate that these functions are essential for tumor growth and progression. The understanding of the exact composition of extracellular HSP90 complexes and the molecular mechanisms at the basis of their functions in the tumor microenvironment may represent the first step to design innovative diagnostic tools and new effective therapies. Here we review the impact of extracellular HSP90 complexes on cancer cell signaling and behavior.

scholarly journals Cytokines and their receptors: molecular mechanism of interleukin-6 gene repression by glucocorticoids.

1992 ◽  
Vol 2 (12) ◽  
pp. S214
Author(s):  
A Ray ◽  
P B Sehgal
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Transplant Patient ◽  
Prognostic Indicator ◽  
Hematopoietic Growth Factors ◽  
Surface Receptors ◽  
Transplant Patients ◽  
Stimulating Factor ◽  
Made In

Recent years have seen the discovery and molecular characterization of a bewildering array of cytokines and hematopoietic growth factors--and an even more complex description of their overlapping functions. The molecular cloning of a wide array of the cell-surface receptors for these cytokines has led to the recognition of classes of structurally related receptor superfamilies. The functional receptors for many of these cytokines (e.g., interleukin (IL)-2R and IL-6R) involve two distinct subunits; strikingly, the same beta subunit can interact with distinct alpha subunits to constitute the receptor for different cytokines (e.g., those for IL-3, IL-5, and granulocyte monocyte colony-stimulating factor). Considerable progress has also been made in defining the molecular mechanisms that underlie clinically relevant cytokine-related phenomena. As an example, the molecular mechanism by which glucocorticoids inhibit IL-6 gene expression has been shown to include the occlusion of the inducible enhancer and the basal promoter elements in the IL-6 promoter. Acute rejection episodes in renal transplant patients are accompanied by increases in serum IL-6 levels; the administration of glucocorticoids during these episodes leads to a rapid and marked decrease in IL-6 levels. It appears that the serum IL-6 level may be a useful diagnostic and prognostic indicator in the transplant patient.

scholarly journals Roles of glycosaminoglycans as regulators of ligand/receptor complexes

Open Biology ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 180026 ◽  
Author(s):  
Robert G. Smock ◽  
Rob Meijers
Keyword(s):  
Cellular Response ◽  
Molecular Mechanisms ◽  
Gag Protein ◽  
Surface Receptors ◽  
Drug Candidates ◽  
Receptor Complexes ◽  
Tumour Metastasis ◽  
Novel Drug

Glycosaminoglycans (GAGs) play a widespread role in embryonic development, as deletion of enzymes that contribute to GAG synthesis lead to deficiencies in cell migration and tissue modelling. Despite the biochemical and structural characterization of individual protein/GAG interactions, there is no concept available that links the molecular mechanisms of GAG/protein engagements to tissue development. Here, we focus on the role of GAG polymers in mediating interactions between cell surface receptors and their ligands. We categorize several switches that lead to ligand activation, inhibition, selection and addition, based on recent structural studies of select receptor/ligand complexes. Based on these principles, we propose that individual GAG polymers may affect several receptor pathways in parallel, orchestrating a cellular response to an environmental cue. We believe that it is worthwhile to study the role of GAGs as molecular switches, as this may lead to novel drug candidates to target processes such as angiogenesis, neuroregeneration and tumour metastasis.

Characterization of early and late cerebral evoke responses (CEP) to stimulation of afferent esophageal pathways in humans

2001 ◽  
Vol 120 (5) ◽  
pp. A630-A630
Author(s):  
C DIENEFELD ◽  
R BECKER ◽  
M KAMATH ◽  
G TOUGAS ◽  
M HAUPTS ◽  
...  
Keyword(s):  
Stimulation Of

scholarly journals Genetic mapping and transcriptomic characterization of a new fuzzless-tufted cottonseed mutant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qian-Hao Zhu ◽  
Warwick Stiller ◽  
Philippe Moncuquet ◽  
Stuart Gordon ◽  
Yuman Yuan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Agronomic Traits ◽  
Gene Families ◽  
Mutant Phenotype ◽  
Wild Type ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Flanking Region ◽  
Comparative Transcriptomic Analysis

Abstract Fiber mutants are unique and valuable resources for understanding the genetic and molecular mechanisms controlling initiation and development of cotton fibers that are extremely elongated single epidermal cells protruding from the seed coat of cottonseeds. In this study, we reported a new fuzzless-tufted cotton mutant (Gossypium hirsutum) and showed that fuzzless-tufted near-isogenic lines (NILs) had similar agronomic traits and a higher ginning efficiency compared to their recurrent parents with normal fuzzy seeds. Genetic analysis revealed that the mutant phenotype is determined by a single incomplete dominant locus, designated N5. The mutation was fine mapped to an approximately 250-kb interval containing 33 annotated genes using a combination of bulked segregant sequencing, SNP chip genotyping, and fine mapping. Comparative transcriptomic analysis using 0–6 days post-anthesis (dpa) ovules from NILs segregating for the phenotypes of fuzzless-tufted (mutant) and normal fuzzy cottonseeds (wild-type) uncovered candidate genes responsible for the mutant phenotype. It also revealed that the flanking region of the N5 locus is enriched with differentially expressed genes (DEGs) between the mutant and wild-type. Several of those DEGs are members of the gene families with demonstrated roles in cell initiation and elongation, such as calcium-dependent protein kinase and expansin. The transcriptome landscape of the mutant was significantly reprogrammed in the 6 dpa ovules and, to a less extent, in the 0 dpa ovules, but not in the 2 and 4 dpa ovules. At both 0 and 6 dpa, the reprogrammed mutant transcriptome was mainly associated with cell wall modifications and transmembrane transportation, while transcription factor activity was significantly altered in the 6 dpa mutant ovules. These results imply a similar molecular basis for initiation of lint and fuzz fibers despite certain differences.

scholarly journals A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1

2021 ◽  
Vol 22 (14) ◽  
pp. 7390
Author(s):  
Nicole Wesch ◽  
Frank Löhr ◽  
Natalia Rogova ◽  
Volker Dötsch ◽  
Vladimir V. Rogov
Keyword(s):  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Biochemical Characterization ◽  
Effective Interaction ◽  
Regulatory Region ◽  
Titration Calorimetry ◽  
Enzymatic Reactions ◽  
Cellular Processes ◽  
Mechanism Of Interaction

Ubiquitin fold modifier 1 (UFM1) is a member of the ubiquitin-like protein family. UFM1 undergoes a cascade of enzymatic reactions including activation by UBA5 (E1), transfer to UFC1 (E2) and selective conjugation to a number of target proteins via UFL1 (E3) enzymes. Despite the importance of ufmylation in a variety of cellular processes and its role in the pathogenicity of many human diseases, the molecular mechanisms of the ufmylation cascade remains unclear. In this study we focused on the biophysical and biochemical characterization of the interaction between UBA5 and UFC1. We explored the hypothesis that the unstructured C-terminal region of UBA5 serves as a regulatory region, controlling cellular localization of the elements of the ufmylation cascade and effective interaction between them. We found that the last 20 residues in UBA5 are pivotal for binding to UFC1 and can accelerate the transfer of UFM1 to UFC1. We solved the structure of a complex of UFC1 and a peptide spanning the last 20 residues of UBA5 by NMR spectroscopy. This structure in combination with additional NMR titration and isothermal titration calorimetry experiments revealed the mechanism of interaction and confirmed the importance of the C-terminal unstructured region in UBA5 for the ufmylation cascade.

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