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DETAILED SLIDE INDEX

  1. 1. Introduction
  2. 2. Physiological roles of Ca2+ signals
  3. 3. Receptor-mediated control of Ca2+ signals
  4. 4. STIM1 and STIM2 are components of SOCs
  5. 5. Orai 1 as component of store operated Ca2+ entry
  6. 6. STIM-Orai coupling details
  7. 7. Transcriptional mechanisms regulating Ca2+
  8. 8. The EGR Family of transcription factors
  9. 9. Wilms tumor suppressor 1 (WT1)
  10. 10. STIM1 expression is dysregulated in Wilms' tumor
  11. 11. STIM1 expression is dependent on WT1 and EGR1
  12. 12. Dysregulation of STIM1 expression in EGR1 KO
  13. 13. ChIP Analysis of the STIM1 promoter
  14. 14. Control of STIM1 expression by WT1 and EGR1
  15. 15. Dynamic EGR1-mediated control of STIM1
  16. 16. Receptor control of EGR1, STIM1/2, PMCA
  17. 17. Altered STIM, PMCA expression alters Ca2+
  18. 18. Inhibition of Ca2+ clearance due to PMCA activity
  19. 19. STIM1-PMCA role in inhibition of Ca2+ clearance
  20. 20. Orai1 activation/PMCA inhibition - STIM1 functions
  21. 21. Polarization of T cells during synapse formation
  22. 22. STIM1 and PMCA co-localize at the site of PHA
  23. 23. Identification of the critical STIM1 domain
  24. 24. STIM1 KD eliminates inhibition of Ca2+ clearance
  25. 25. Local control of cytosolic Ca2+ content (1)
  26. 26. Global control of Ca2+ clearance after STIM1 KD
  27. 27. Local control of cytosolic Ca2+ content (2)
  28. 28. Remodeling of Ca2+ homeostasis at synapse
  29. 29. Acknowledgements
  30. 30. END

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TALK'S CITATION

Soboloff, J. (2013), "Mechanisms Regulating STIM Expression and Function in Ca2+ Signaling", in Simpson, A. (ed.), Calcium Signaling I: Regulation, Mechanisms, Effectors, Role in Disease and Recent Advances, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/?t=BL0293385)

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ABOUT THIS TALK

Speaker(s)

Dr. Jonathan Soboloff Show Biography

SPEAKER BIOGRAPHY

Dr. Jonathan Soboloff – Temple University School of Medicine, USA

Jonathan Soboloff is an Assistant Professor in the Department of Biochemistry at the Temple University School of Medicine. He received his PhD at the University of Ottawa in Physiology, followed by Postdoctoral training at the University of Toronto and the University of Maryland. Jonathan's research has focused on Ca2+ signaling in numerous different cell types although current research is focused on multiple aspects of STIM1 function in immune cells.

Publication Date

February, 2013

Topics Covered

Basic concepts and physiological implications... more

TOPICS COVERED IN THIS TALK

  • Basic concepts and physiological implications
  • Transcriptional mechanisms in control of STIM1 expression
  • Dynamic receptor-mediated STIM1 upregulation
  • Delayed Ca2+ clearance during T cell activation
  • Role of STIM1 in this process

Series

Calcium Signaling I

OTHER TALKS IN THIS SERIES

INTRODUCTION TO CALCIUM SIGNALING
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TOPICS COVERED IN THIS TALK

  • Introduction to the spatial and temporal complexity of cellular calcium signals
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TOPICS COVERED IN THIS TALK

  • Introduction to Calcium homeostasis
  • Synthetic fluorescent Calcium probes
  • Ratiometric and non-ratiometric probes
  • Calibration
  • Recombinant probes: the targeted probes
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  • Wide dynamic range
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TOPICS COVERED IN THIS TALK

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  • How to study complex biology
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  • GcaMPs
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  • Real-time cardiac activation
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  • Heart development
  • Cell based therapy and coupling
  • Embryonic stem cells and GCaMPs
  • Vascular control and pulsars
  • Future directions
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Prof. Eduardo Ríos

TOPICS COVERED IN THIS TALK

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  • Calcium movements
  • Movements of Ions and Solutes
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CALCIUM INFLUX
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TOPICS COVERED IN THIS TALK

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  • Stim1
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TOPICS COVERED IN THIS TALK

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TOPICS COVERED IN THIS TALK

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CALCIUM RELEASE
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12. The Molecular Biology of the Inositol Trisphosphate Receptor More info
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TOPICS COVERED IN THIS TALK

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TOPICS COVERED IN THIS TALK

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  • Channel mechanisms that account for graded Ca2+ release
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TOPICS COVERED IN THIS TALK

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TOPICS COVERED IN THIS TALK

  • Calcium release from intracellular stores as opposed to Calcium entry from the external solution
  • The pioneers of Calcium signaling
  • Patch clamp recording combined with optical Calcium measurements
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  • Different Calcium releasing messengers
  • Calcium-mediated NO release
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  • Stimulusmetabolism coupling
  • Calcium release from the endoplasmic reticulum and from acid stores
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Play '17. Ryanodine Receptors and Cardiac Function'
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Prof. David Eisner

TOPICS COVERED IN THIS TALK

  • Introduction to Calcium cycling in the heart
  • How to measure SR and sarcolemmal Calcium fluxes
  • What controls SR Calcium content
  • The effects of changing the open probability of the RyR
  • The link between Calcium and arrhythmias
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CALCIUM EFFLUX AND SEQUESTRATION
Play '18. The Plasma Membrane Calcium Pump: Biochemistry, Physiology and Molecular Pathology'
18. The Plasma Membrane Calcium Pump: Biochemistry, Physiology and Molecular Pathology More info
Prof. Ernesto Carafoli

TOPICS COVERED IN THIS TALK

  • Targets of the signaling function of calcium
  • Decoding of the calcium message by specific calcium binding proteins
  • Control of calcium in the cell by calcium transporting proteins in the membranes
  • Calcium pumps: biochemistry, molecular biology, structure and regulation
  • Similarities in the regulation mechanisms between the two major pumps, that in the endoplasmic reticulum and that in the plasma membrane
  • Ambivalence of the calcium signal
  • Calcium signaling defects and related pathologies
  • Genetic defects of the plasma membrane calcium pumps in hereditary deafness
Play '19. The Calcium Saga: A Matter of Life and Death'
19. The Calcium Saga: A Matter of Life and Death More info
Prof. Pierluigi Nicotera

TOPICS COVERED IN THIS TALK

  • Calcium and cytotoxicity
  • Indicator dyes for calcium detection
  • Alteration of thiol and calcium homeostasis causes cell death
  • Oxidative stress and thiol modification impair calcium storage and extrusion
  • Calcium ATPase
  • The calcium and thiol hypothesis of cell death
  • Calcium as a second messenger
  • Calcium is involved in different cell death paradigms
  • Nuclear calcium transport
  • Intracellular calcium distribution
  • PMCAs: vital membrane calcium transporters
  • PMCAs are degraded during cell death
  • Non-degradable PMCAs protect against cell death
  • Mechanisms of calcium deregulation during cell death
  • NCX3 and calpains in calcium maintenance
  • Prevention of excitotoxicity via calcium management
Play '20. Sodium-Calcium Exchange'
20. Sodium-Calcium Exchange More info
Prof. John Reeves

TOPICS COVERED IN THIS TALK

  • The definition and thermodynamic driving forces for Na/Ca exchange and the historical development of the field
  • The molecular biology of Na/Ca exchange family members
  • The regulation of Na/Ca exchange
  • The physiological functions of Na/Ca exchange in cardiac physiology, hypertension and higher neural functions
Play '21. Ca2+ Efflux and Ca2+ Signals'
21. Ca2+ Efflux and Ca2+ Signals More info
Dr. Anne Green

TOPICS COVERED IN THIS TALK

  • Introduction to [Calcium]c oscillations
  • Involvement of Calcium fluxes in [Calcium]c oscillations
  • Plasma membrane Calcium efflux
  • Impact of Calcium efflux inhibition on [Calcium]c oscillations
  • Mini-glucagon as a physiological Calcium efflux inhibitor
  • Atrial natriuretic peptide as a physiological Calcium efflux stimulator
  • A hypothetical mechanism for plasma membrane Calcium flux as a determinant of [Calcium]c oscillation frequency
  • 'Calcium efflux modulators': a class of physiological agonists?
ORGANELLE CALCIUM
Play '22. Regulation and Role of Mitochondrial Ca2+ Homeostasis'
22. Regulation and Role of Mitochondrial Ca2+ Homeostasis More info
Prof. Rosario Rizzuto

TOPICS COVERED IN THIS TALK

  • Targeted Calcium indicators
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  • The mitochondrial Calcium uniporter of the inner membrane (MCU)
  • The ER-mitochondria contacts
  • Calcium re-extrusion
  • ATP measurements
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Play '23. Peroxisomes and Golgi apparatus as players in Ca2+ homeostasis'
23. Peroxisomes and Golgi apparatus as players in Ca2+ homeostasis More info
Dr. Paola Pizzo
Dr. Alex Costa

TOPICS COVERED IN THIS TALK

  • Role of Peroxisomes and Golgi apparatus within the cell
  • Methodologies to study peroxisomal and Golgi apparatus Ca2+ signals
  • Ca2+ handling by mammalian and plant peroxisomes and its functional role
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Play '24. Organellar Calcium Pumps of the Golgi and ER: From Yeast to Human'
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TOPICS COVERED IN THIS TALK

  • Early and current views on Calcium signaling
  • Phylogenetic tree of Calcium-ATPases
  • Identification of a new family of Golgi/secretory pathway Calcium-ATPases (SPCA)
  • Why have a Calcium pump in the Golgi?
  • Yeast as a model to understand Golgi Calcium pumps
  • Biochemical characterization of Calcium and Mn2+ transport
  • Phenotype screening in yeast to identify residues important for ion transport and selectivity in Pmr1
  • Structural and homology models of Calcium-ATPases
  • Golgi pumps in mammals
  • From structure to physiology
  • Haploinsufficiency of ATP2C1 leads to Hailey Hailey disease
  • Insights from yeast
  • Distribution and localization of SPCA1 and SPCA2
Play '25. Ca2+ Dynamics Between Mitochondria and the Endoplasmic Reticulum'
25. Ca2+ Dynamics Between Mitochondria and the Endoplasmic Reticulum More info
Dr. Wolfgang Graier

TOPICS COVERED IN THIS TALK

  • 3D structure of the endoplasmic reticulum and mitochondria
  • Techniques to measure organelle calcium
  • Mitochondrial functions
  • Principles of mitochondrial calcium signaling
  • Functional coupling of the endoplasmic reticulum and the mitochondria
  • Consequences of alterations in the structural integrity of the mitochondria
  • Subplasmalemmal mitochondrial calcium buffering
  • Physiological importance of mitochondrial calcium uptake
  • The cellular calcium cycle
Play '26. Nuclear Calcium Signaling'
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Dr. Oleg Gerasimenko
Dr. Julia Gerasimenko

TOPICS COVERED IN THIS TALK

  • Nuclear calcium signaling, an intriguing history of the last 10 years of research and promising recent developments with the emphasis on fluorescent confocal techniques
  • Basic features and major consensus on principles
  • Uncertainty about nuclear calcium independence
  • New data on the elusive NAADP receptor
SPATIOTEMPORAL CALCIUM SIGNALS
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Prof. Ian Parker

TOPICS COVERED IN THIS TALK

  • Calcium as a life and death cellular messenger
  • Sequestration and liberation of calcium from the endoplasmic reticulum
  • Calcium release through inositol trisphosphate receptors and modulation by calcium
  • Optical techniques to visualize and stimulate intracellular calcium signals
  • 'Elementary' calcium signals through single channels and clusters of channels
  • Generation of periodic calcium waves by stochastic elementary events
  • Modulation of calcium signals by calcium binding proteins
  • The hierarchical organization of cellular calcium signals
Play '28. Regulation of Intracellular Calcium Signaling, Localized Signals and Oscillations'
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Prof. Barbara Ehrlich

TOPICS COVERED IN THIS TALK

  • Calcium as a trigger for many cellular events including muscle contraction, hormone secretion and cell growth
  • The release of calcium from intracellular stores using electrophysiological, biochemical and molecular techniques combined with imaging
  • Regulation by chromogranin, a protein that binds to the major calcium release channel, the InsP3R
  • Regulation by a steroid hormone both at physiological and supra-physiological levels
  • Regulation by a protein tyrosine phosphatase SHP-2
  • The consequences of mutations or non-physiological modulations of each pathway
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Dr. David Friel

TOPICS COVERED IN THIS TALK

  • Introduction to quantitative descriptions of Calcium signaling
  • Examples of Calcium signals in sympathetic neurons
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  • Methods for quantifying Calcium handling in intact cells
  • Analysis of Calcium dynamics in sympathetic neurons
Play '30. Calcium Flickers Steer Cell Migration'
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Prof. Heping Cheng

TOPICS COVERED IN THIS TALK

  • Paradox of calcium signaling in cell migration
  • Calcium flickers in migrating fibroblasts
  • Trigger mechanism and molecular origin of calcium flickers
  • Calcium flickers steer cell turning
  • Feedback loop between calcium flickers and cytoskeletal traction force generation
  • Role of calcium flickers in chemotaxis
  • Calcium flicker model of cell turning
CALCIUM EFFECTORS
Play '31. Calcium, Calmodulin and Calcineurin'
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Prof. Stephen Bolsover

TOPICS COVERED IN THIS TALK

  • Calmodulin is highly conserved
  • Calmodulin structure
  • EF hand proteins
  • Calcium binding
  • Calmodulin targets
  • Mechanism of calmodulin action
  • Calmodulin-dependent protein kinases
  • Calmodulin dependent protein kinase II autonomy
  • Calcineurin structure and activation
  • Action of cyclosporin
  • NFAT signaling
  • Phosphatases downstream of calcineurin
  • Differential responses of calmodulin-dependent protein kinase II and calcineurin to calcium signals
Play '32. Ca2+ and the Regulation of Small GTPases'
32. Ca2+ and the Regulation of Small GTPases More info
Prof. Peter Cullen

TOPICS COVERED IN THIS TALK

  • Introduction to small GTPases
  • Ras as a GTPase subfamily
  • Molecular entities, Ras GEFs and Ras GAPs, that couple Calcium to Ras activation
  • Temporal aspects of Calcium coupling to Ras activation, using the Calcium-regulated Ras GAPs CAPRI and RASAL as examples of amplitude and frequency Calcium sensors
  • Calcium as a messenger allowing Ras activation on endomembranes
  • Calcium coupling to Ras in physiology and disease
Play '33. Neuronal Calcium Sensor Proteins: Calcium Sensors and Regulators of Diverse Cellular Functions'
33. Neuronal Calcium Sensor Proteins: Calcium Sensors and Regulators of Diverse Cellular Functions More info
Prof. Bob Burgoyne

TOPICS COVERED IN THIS TALK

  • Introduction to calcium sensors
  • The neuronal calcium sensor (NCS) protein family
  • The calcium/myristoyl switch
  • Dynamics of hippocalcin translocation
  • Specific localization of NCS proteins
  • Functions of NCS-1
  • Hippocalcin in synaptic plasticity
  • KChIP proteins in traffic of potassium channels
  • Molecular targets of NCS proteins
  • The unique features of the NCS family
Play '34. Calcium-Regulated Adenylyl Cyclases and Cyclic AMP Compartmentalization'
34. Calcium-Regulated Adenylyl Cyclases and Cyclic AMP Compartmentalization More info
Prof. Dermot Cooper

TOPICS COVERED IN THIS TALK

  • Calcium-entry
  • Elements of the compartment: adenylyl cyclases, lipid rafts, PP2A, NHE1, calmodulin and PDE
  • cAMP kinetics within the compartment in single cells: role of PDE4, PKA and AKAPs
  • cAMP oscillations
Play '35. Calcium and transcription-coupling'
35. Calcium and transcription-coupling More info
Dr. Karen Lounsbury

TOPICS COVERED IN THIS TALK

  • Calcium sources
  • Calcium-regulated transcription factors: Calcium/cAMP response element binding protein (CREB), nuclear factor of activated T-cells (NFAT) and serum response factor (SRF)
  • Calcium signaling cascades
  • Calcium and cell differentiation
  • Calcium and disease
Play '36. Cellular calcium (Ca2+) buffers'
36. Cellular calcium (Ca2+) buffers More info
Prof. Dr. Beat Schwaller

TOPICS COVERED IN THIS TALK

  • The Ca2+ signaling toolkit
  • The EF-hand family of Ca2+-binding proteins
  • Biophysical properties of Ca2+ buffers determine their function
  • Ca2+ buffers as intracellular Ca2+ signal modulators
  • The «slow» buffer parvalbumin (PV) affects fast-twitch muscle function
  • Ca2+ buffers modulate short-term plasticity of synaptic transmission
  • Phenotypes of Ca2+ buffer knockout mice
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37. Extracellular calcium signaling More info
Dr. Aldebaran M. Hofer

TOPICS COVERED IN THIS TALK

  • Local accumulations and depletions of extracellular Calcium
  • Systemic Calcium homeostasis
  • Extracellular Ca2+ sensing receptor (CaR)
  • Mutations in the human CaR
  • How and when Calcium fluctuates locally
  • Calcium fluxes across the plasma membrane during calcium signals can be significant
  • Oscillations in external Calcium
  • Ca2+ selective microelectrodes
  • The effect of Carbachol
  • Ways in which local [Ca2+]out can change
  • Extracellular Ca2+ "sensors"
  • Ca2+ as a paracrine messenger
  • Ca2+ as a local extracellular messenger
  • Co-culture model system
  • Ca2+ as an autocrine signaling molecule
  • Evidence for the physiological importance of fluctuations in [Ca2+]out
  • [Ca2+]out affects alkaline secretion
Play '38. Ca2+, fertilization and egg activation'
38. Ca2+, fertilization and egg activation More info
Prof. Karl Swann

TOPICS COVERED IN THIS TALK

  • The role of Ca2+ in activating development in eggs of all species
  • Sperm egg fusion as the event that precedes the Ca2+ signal
  • Evidence for a sperm factor that triggers Ca2+ release
  • Discovery of PLCzeta as sperm factor in mammals
  • Mechanism of Ca2+ oscillations triggered by PLCzeta
Play '39. Calcium regulation of transcription in plants'
39. Calcium regulation of transcription in plants More info
Prof. Hillel Fromm

TOPICS COVERED IN THIS TALK

  • Calcium as a ubiquitous second messenger
  • Evolution and status in plant cells
  • Calmodulin as a transducer of Calcium signals
  • Mechanisms of transcription regulation by Calcium
  • Calmodulin-binding transcription activators
  • Calcium regulation of transcription in defense responses
  • CAMTA and regulation of growth and stress responses
Play '40. Automated Ca2+ imaging of chemosensory neurones in C.elegans'
40. Automated Ca2+ imaging of chemosensory neurones in C.elegans More info
Dr. Nikos Chronis

TOPICS COVERED IN THIS TALK

  • What C. elegans are
  • Neuronal networks: from stimulation to behavior
  • Monitoring neuronal activity
  • Automating In vivo Ca imaging
  • An automated calcium imaging platform
  • A microfluidic chip
  • Processing single worms
  • Fabrication
  • Automated single worm processing on-chip
  • Automated calcium imaging on-chip
  • A typical Ca response (chemosensory neuron)
  • Effects of age on the function of sensory neurons
  • Parameters
  • Initial intracellular Ca level may be age-dependent
  • Calcium pathway in ASH neuron
  • Using in vivo imaging for drug screening
  • Drug-treated vs. untreated worms
Now Playing
41. Mechanisms Regulating STIM Expression and Function in Ca2+ Signaling
Dr. Jonathan Soboloff
Play '42. Dynamic signal encoding in the S. cerevisiae calcium response'
42. Dynamic signal encoding in the S. cerevisiae calcium response More info
Dr. Chiraj Dalal

TOPICS COVERED IN THIS TALK

  • Calcium and Signaling
  • Excessive calcium causes cellular stress
  • Signaling pathways are turned on to combat this stress
  • In budding yeast, these pathways involve nuclear translocation of transcriptional regulator Crz1
  • Examination of this regulator shows that nuclear translocation occurs in "bursts"
  • Bursts are quantized and frequency-modulated
  • Frequency modulation enables proportional expression of downstream target genes
CALCIUM AND DISEASE
Play '43. Polycystins, Calcium Signaling and Pathogenesis of Polycystic Kidney Disease'
43. Polycystins, Calcium Signaling and Pathogenesis of Polycystic Kidney Disease More info
Prof. Laura del Senno

TOPICS COVERED IN THIS TALK

  • Clinical and genetic aspects of polycystic kidney disease
  • The polycystins (PC1, PC2)
  • The PC2 channel
  • PC1 and PC2 subcellular location and interaction
  • Mechanosensory function of the ciliary PC1/PC2 complex
  • PC signaling and calcium homeostasis
  • PC1, calcium levels and cell proliferation
  • PC1, cAMP signaling and cell proliferation
  • PCs and physiopathologic calcium signaling
Play '44. Ca2+ Alterations in Familial Alzheimer's Disease (FAD)'
44. Ca2+ Alterations in Familial Alzheimer's Disease (FAD) More info
Dr. Paola Pizzo

TOPICS COVERED IN THIS TALK

  • Introduction to Alzheimer's disease
  • Morphological and functional features
  • Genetic studies
  • Presenilin functions and calcium homeostasis
  • Calcium dyshomeostasis and FAD
  • Modulatory role of presenilin on IP3-evoked Calcium release
  • Different effects of PS mutants on intracellular Calcium stores
  • A reformulation of the 'Calcium hypothesis' for FAD
Play '45. Pancreatitis and Calcium Signaling'
45. Pancreatitis and Calcium Signaling More info
Prof. Ole Petersen

TOPICS COVERED IN THIS TALK

  • Normal Calcium signaling events in pancreatic acinar cells
  • Hyperstimulation as a cause of sustained global elevation of the cytosolic [Calcium], Calcium-dependent vacuolization and Calcium-dependent protease activation
  • Bile acids causing sustained global Calcium signals and necrosis
  • Calcium-dependent necrosis evoked by non-oxidative alcohol metabolites (fatty acid ethyl esters and fatty acids) but not by alcohol or acetaldehyde
  • The mechanism of action of fatty acid ethyl esters and fatty acids
  • The mildly protective effect of coffee (caffeine)
  • A model for the initiation of alcoholic pancreatitis
Play '46. Mechanism-Based Therapies for Heart Failure and Cardiac Arrhythmias'
46. Mechanism-Based Therapies for Heart Failure and Cardiac Arrhythmias More info
Prof. Andrew Marks

TOPICS COVERED IN THIS TALK

  • Introduction to excitation-contraction coupling
  • History of the field of EC coupling
  • Introduction to the ryanodine receptor/calcium release channel (RyR2)
  • Mechanisms that regulate the RyR2 channel during stress
  • Defective regulation of RyR2 in heart failure
  • Evidence that diastolic sarcoplasmic reticulum (SR) calcium leak causes heart failure and arrhythmias in vivo
  • Novel therapeutic approaches to treating heart failure and preventing sudden cardiac death by fixing the leak in RyR2 channels
Play '47. Genetic Defects and Calcium'
47. Genetic Defects and Calcium More info
Prof. Tullio Pozzan

TOPICS COVERED IN THIS TALK

  • General concepts of calcium signaling
  • Mechanisms of calcium extrusion/uptake
  • Mechanisms of calcium release from the ER/SR
  • General concepts about plasma membrane calcium channels
  • Genetic defects of calcium release channels
  • Genetic defects of plasma membrane calcium channels
  • Genetic defects of calcium pumps
  • Novel findings on genetic defects of store dependent calcium channels

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