scholarly journals Orphan Receptor GPR179 Forms Macromolecular Complexes With Components of Metabotropic Signaling Cascade in Retina ON-Bipolar Neurons

2013 ◽  
Vol 54 (10) ◽  
pp. 7153 ◽  
Author(s):  
Cesare Orlandi ◽  
Yan Cao ◽  
Kirill A. Martemyanov
Keyword(s):  
Orphan Receptor ◽  
Signaling Cascade ◽  
Macromolecular Complexes ◽  
Metabotropic Signaling

Targeting Post-Translational Remodeling of Ryanodine Receptor: A New Track for Alzheimer's Disease Therapy?

2020 ◽  
Vol 17 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Mounia Chami ◽  
Frédéric Checler
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Complex Structure ◽  
Ryanodine Receptors ◽  
Therapeutic Window ◽  
Signaling Cascade ◽  
Macromolecular Complex ◽  
Macromolecular Complexes

Pathologic calcium (Ca2+) signaling linked to Alzheimer’s Disease (AD) involves the intracellular Ca2+ release channels/ryanodine receptors (RyRs). RyRs are macromolecular complexes where the protein-protein interactions between RyRs and several regulatory proteins impact the channel function. Pharmacological and genetic approaches link the destabilization of RyRs macromolecular complexes to several human pathologies including brain disorders. In this review, we discuss our recent data, which demonstrated that enhanced neuronal RyR2-mediated Ca2+ leak in AD is associated with posttranslational modifications (hyperphosphorylation, oxidation, and nitrosylation) leading to RyR2 macromolecular complex remodeling, and dissociation of the stabilizing protein Calstabin2 from the channel. We describe RyR macromolecular complex structure and discuss the molecular mechanisms and signaling cascade underlying neuronal RyR2 remodeling in AD. We provide evidence linking RyR2 dysfunction with β-adrenergic signaling cascade that is altered in AD. RyR2 remodeling in AD leads to histopathological lesions, alteration of synaptic plasticity, learning and memory deficits. Targeting RyR macromolecular complex remodeling should be considered as a new therapeutic window to treat/or prevent AD setting and/or progression.

Imaging of platinum-shadowed macromolecular complexes in dark field

1984 ◽  
Vol 42 ◽  
pp. 146-147
Author(s):  
D.W. Andrews ◽  
F.P. Ottensmeyer
Keyword(s):  
Thin Film ◽  
Three Dimensional ◽  
Average Diameter ◽  
Dark Field ◽  
Bright Field ◽  
Field Mode ◽  
Macromolecular Complexes ◽  
Average Mass ◽  
Topological Features ◽  
Projection Images

Shadowing with heavy metals has been used for many years to enhance the topological features of biological macromolecular complexes. The three dimensional features present in directionaly shadowed specimens often simplifies interpretation of projection images provided by other techniques. One difficulty with the method is the relatively large amount of metal used to achieve sufficient contrast in bright field images. Thick shadow films are undesirable because they decrease resolution due to an increased tendency for microcrystalline aggregates to form, because decoration artefacts become more severe and increased cap thickness makes estimation of dimensions more uncertain.The large increase in contrast provided by the dark field mode of imaging allows the use of shadow replicas with a much lower average mass thickness. To form the images in Fig. 1, latex spheres of 0.087 μ average diameter were unidirectionally shadowed with platinum carbon (Pt-C) and a thin film of carbon was indirectly evaporated on the specimen as a support.

Semi-automated methods for 3-D reconstruction of macromolecular complexes

1995 ◽  
Vol 53 ◽  
pp. 42-43
Author(s):  
B. Carragher ◽  
M. Whittaker
Keyword(s):  
Three Dimensional ◽  
Time Saving ◽  
Macromolecular Complexes ◽  
Symmetry Properties ◽  
Dimensional Reconstruction ◽  
Experienced Operator ◽  
Projection Images ◽  
The Individual ◽  
Natural Symmetry

Techniques for three-dimensional reconstruction of macromolecular complexes from electron micrographs have been successfully used for many years. These include methods which take advantage of the natural symmetry properties of the structure (for example helical or icosahedral) as well as those that use single axis or other tilting geometries to reconstruct from a set of projection images. These techniques have traditionally relied on a very experienced operator to manually perform the often numerous and time consuming steps required to obtain the final reconstruction. While the guidance and oversight of an experienced and critical operator will always be an essential component of these techniques, recent advances in computer technology, microprocessor controlled microscopes and the availability of high quality CCD cameras have provided the means to automate many of the individual steps.During the acquisition of data automation provides benefits not only in terms of convenience and time saving but also in circumstances where manual procedures limit the quality of the final reconstruction.

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