Advances in the Visualization of Molecular Assemblies Within Cellular Signaling Nanodomains: Insights From a Decade of Mapping of Ryanodine Receptor Clusters

2018 ◽  
pp. 167-197
Author(s):  
Isuru Jayasinghe ◽  
Alexander H. Clowsley ◽  
Christian Soeller
Keyword(s):  
Ryanodine Receptor ◽  
Cellular Signaling ◽  
Molecular Assemblies ◽  
Receptor Clusters

scholarly journals Loss of dysferlin or myoferlin results in differential defects in excitation–contraction coupling in mouse skeletal muscle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David Y. Barefield ◽  
Jordan J. Sell ◽  
Ibrahim Tahtah ◽  
Samuel D. Kearns ◽  
Elizabeth M. McNally ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Calcium Binding ◽  
Physiological Role ◽  
Muscle Disease ◽  
Calcium Handling ◽  
Membrane Repair ◽  
Tubule Formation ◽  
Ec Coupling ◽  
Associated Proteins ◽  
Receptor Clusters

AbstractMuscular dystrophies are disorders characterized by progressive muscle loss and weakness that are both genotypically and phenotypically heterogenous. Progression of muscle disease arises from impaired regeneration, plasma membrane instability, defective membrane repair, and calcium mishandling. The ferlin protein family, including dysferlin and myoferlin, are calcium-binding, membrane-associated proteins that regulate membrane fusion, trafficking, and tubule formation. Mice lacking dysferlin (Dysf), myoferlin (Myof), and both dysferlin and myoferlin (Fer) on an isogenic inbred 129 background were previously demonstrated that loss of both dysferlin and myoferlin resulted in more severe muscle disease than loss of either gene alone. Furthermore, Fer mice had disordered triad organization with visibly malformed transverse tubules and sarcoplasmic reticulum, suggesting distinct roles of dysferlin and myoferlin. To assess the physiological role of disorganized triads, we now assessed excitation contraction (EC) coupling in these models. We identified differential abnormalities in EC coupling and ryanodine receptor disruption in flexor digitorum brevis myofibers isolated from ferlin mutant mice. We found that loss of dysferlin alone preserved sensitivity for EC coupling and was associated with larger ryanodine receptor clusters compared to wildtype myofibers. Loss of myoferlin alone or together with a loss of dysferlin reduced sensitivity for EC coupling, and produced disorganized and smaller ryanodine receptor cluster size compared to wildtype myofibers. These data reveal impaired EC coupling in Myof and Fer myofibers and slightly potentiated EC coupling in Dysf myofibers. Despite high homology, dysferlin and myoferlin have differential roles in regulating sarcotubular formation and maintenance resulting in unique impairments in calcium handling properties.

Analysis of Dihydropyridine and Ryanodine Receptor Clusters in Healthy and Failing Human Cardiac Myocytes

2008 ◽  
Vol 17 ◽  
pp. S232
Author(s):  
David Crossman ◽  
Christian Soeller ◽  
Peter Ruygrok ◽  
Mark Cannell
Keyword(s):  
Cardiac Myocytes ◽  
Ryanodine Receptor ◽  
Receptor Clusters

scholarly journals 3D Dstorm Imaging Reveals Camkii-Dependent Dispersal of Ryanodine Receptor Clusters in Failing Rat Cardiomyocytes

2020 ◽  
Vol 118 (3) ◽  
pp. 529a-530a
Author(s):  
Xin Shen ◽  
Terje R. Kolstad ◽  
Jonas van den Brink ◽  
Michael Frisk ◽  
Yufeng Hou ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Rat Cardiomyocytes ◽  
Receptor Clusters

scholarly journals Simultaneous Detection and Colocalization of Calcium Sparks and Ryanodine Receptor Clusters in Cardiac Myocytes

2015 ◽  
Vol 108 (2) ◽  
pp. 262a
Author(s):  
Alex Vallmitjana ◽  
Florian Hiess ◽  
S.R. Wayne Chen ◽  
Leif Hove-Madsen ◽  
Raul Benitez
Keyword(s):  
Cardiac Myocytes ◽  
Ryanodine Receptor ◽  
Simultaneous Detection ◽  
Calcium Sparks ◽  
Receptor Clusters

scholarly journals Analysis of ryanodine receptor clusters in rat and human cardiac myocytes

2007 ◽  
Vol 104 (38) ◽  
pp. 14958-14963 ◽  
Author(s):  
C. Soeller ◽  
D. Crossman ◽  
R. Gilbert ◽  
M. B. Cannell
Keyword(s):  
Cardiac Myocytes ◽  
Ryanodine Receptor ◽  
Receptor Clusters

Nanoscale analysis of ryanodine receptor clusters in dyadic couplings of rat cardiac myocytes

2015 ◽  
Vol 80 ◽  
pp. 45-55 ◽  
Author(s):  
Yufeng Hou ◽  
Isuru Jayasinghe ◽  
David J. Crossman ◽  
David Baddeley ◽  
Christian Soeller
Keyword(s):  
Cardiac Myocytes ◽  
Ryanodine Receptor ◽  
Receptor Clusters ◽  
Rat Cardiac Myocytes

scholarly journals 3D visualisation of the cardiac ryanodine receptor clusters and the molecular-scale fraying of dyads

2021 ◽  
Author(s):  
Thomas M. D. Sheard ◽  
Miriam E. Hurley ◽  
Andrew J Smith ◽  
John Colyer ◽  
Ed White ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Ryanodine Receptor ◽  
Ventricular Myocytes ◽  
Three Dimensional ◽  
Super Resolution ◽  
Structural Protein ◽  
3D Visualisation ◽  
Central Regions ◽  
Molecular Machinery ◽  
Receptor Clusters

Clusters of ryanodine receptor calcium channels (RyRs) form the primary molecular machinery in cardiomyocytes. Various adaptations of super-resolution microscopy have revealed intricate details of the structure, molecular composition and locations of these couplons. However, most optical super-resolution techniques lack the capacity for three-dimensional (3D) visualisation. Enhanced Expansion Microscopy (EExM) offers resolution (in-plane and axially) sufficient to spatially resolve individual proteins within peripheral couplons and within dyads located in the interior. We have combined immunocytochemistry and immunohistochemistry variations of EExM with 3D visualisation to examine the complex topologies, geometries and molecular sub-domains within RyR clusters. We observed that peripheral couplons exhibit variable co-clustering ratios and patterns between RyR and the structural protein, junctophilin-2 (JPH2). Dyads possessed sub-domains of JPH2 which occupied the central regions of the RyR cluster, whilst the poles were typically devoid of JPH2 and broader, and likely specialise in turnover and remodelling of the cluster. In right ventricular myocytes from rats with monocrotaline-induced right ventricular failure, we observed hallmarks of RyR cluster fragmentation accompanied by similar fragmentations of the JPH2 sub-domains. We hypothesise that the frayed morphology of RyRs in close proximity to fragmented JPH2 structural sub-domains may form the primordial foci of RyR mobilisation and dyad remodelling.

scholarly journals Distribution and Function of Cardiac Ryanodine Receptor Clusters in Live Ventricular Myocytes

2015 ◽  
Vol 290 (33) ◽  
pp. 20477-20487 ◽  
Author(s):  
Florian Hiess ◽  
Alexander Vallmitjana ◽  
Ruiwu Wang ◽  
Hongqiang Cheng ◽  
Henk E. D. J. ter Keurs ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Ventricular Myocytes ◽  
Receptor Clusters ◽  
And Function ◽  
Cardiac Ryanodine Receptor

scholarly journals Junctophilin-2 in the nanoscale organisation and functional signalling of ryanodine receptor clusters in cardiomyocytes

2016 ◽  
Vol 129 (23) ◽  
pp. 4388-4398 ◽  
Author(s):  
Michelle L. Munro ◽  
Isuru D. Jayasinghe ◽  
Qiongling Wang ◽  
Ann Quick ◽  
Wei Wang ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Receptor Clusters

scholarly journals Analysis of Cav1.2 and Ryanodine Receptor Clusters in Rat Ventricular Myocytes

2010 ◽  
Vol 99 (12) ◽  
pp. 3923-3929 ◽  
Author(s):  
David R.L. Scriven ◽  
Parisa Asghari ◽  
Meredith N. Schulson ◽  
Edwin D.W. Moore
Keyword(s):  
Ryanodine Receptor ◽  
Ventricular Myocytes ◽  
Rat Ventricular Myocytes ◽  
Receptor Clusters
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