calcium signaling Flashcards
Cytoplasmic Ca2+ buffers are proteins that bind to
free Ca2+ in the cell.
cytoplasmic Ca2+ protein buffers function to
restrict the spatial spread of free Ca2+ in order to localize calcium and control signaling pathways that depend upon calcium concentrations.
Buffers also store:
Ca2+ until it can be properly transported
After calcium ions are released from their effectors, buffers sequester them until they are
transported out of the cell, which is a relatively slow process.
Calcium ions are released from the ER/SR into the cytoplasm through
calcium channels mediated by ryanodine and inositol triphosphated (IP3) receptors.
Recognition of Ca2+ in the cytoplasm by _____ receptors triggers the ____.
ryanodine
release of Ca2+ from the ER/SR
This is a positive feedback mechanism:
the release of calcium ions is sensed by the receptors, leading to _____.
further calcium release
IP3 receptors respond to
IP3 (a secondary messenger in a G-coupled protein receptor signaling pathway) to activate Ca2+ channels and stimulate Ca2+ influx into the cytoplasm from the ER/SR.
Calcium ions are extruded from cytoplasm into the extracellular space or the lumen of the ER/SR
by Ca2+ pumps that hydrolyze ATP.
Ca2+ pump is called:
- In cell membrane:
- In the SR/ER:
Plasma Membrane Ca2+ ATPase (PMCa ATPase)
Sarco/Endoplamic Reticulum Ca2+ ATPase
(SERCa ATPase).
EF hands and C2 domains are _____.
structural motifs that depend on coordination with calcium ions
EF hand structure:
EF hands are helix-loop-helix domains with two perpendicular alpha helices connected by a short loop that coordinates with calcium ions.
Calmodulin is a protein made up of
4 EF hands
C2 domains are
structural domains on proteins that target the protein to the cell membrane.
______ has a C2 domain.
Protein Kinase A
The C2 domain coordinates with
2 or 3 calcium ions.
Other calcium ion effectors have
EF-hand domains and many other proteins that bind with plasma membranes contain C2 domains (such as synaptotagmin ,which is involved in neurotransmitter release).
synaptotagmin is involved in
neurotransmitter release
Fundamentals governing calcium as a cell signal
- Sources and Sinks for Calcium
- Movements in/out of Sources/Sinks
- Cellular Calcium Buffers
- Calcium Effectors
onset of Ca2+ signals is ____
far more rapid than that of other signals.
Movement from sources into cytoplasm
- Ion Channels
- Plasma membrane:
- ER/SR, (nuclear envelope):
- Mitochondria
Movement of sources of Calcium Ion Channels
move passive, electrochemically downhill
Movement of sources of Calcium:
Plasma Membrane
- Voltage- and ligand-gated Ca2+ channels
- store-operated Ca2+ channels (Orai1).
- Ca2+ moves from outside cell into cytoplasm
Movement of sources of calcium: ER/SR (nuclear envelope):
- IP3 receptors
- ryanodine receptors.
- Ca2+ moves from lumen of ER/SR to cytoplasm
Movement of sources of calcium: Mitochondria
- Mitochondrial uniporter
- permeability transition pore (MPTP)
- Direction depends on Ca2+ gradient.
- MPTP contributes to cell death during stroke and myocardial infarction.
Movement from cytoplasm into sinks
- Transporters (active, against electrochemical gradient)
- Ca2+ pumps use ATP to move Ca2+ out of cytoplasm into extracellular space (PMCA pumps) or into lumen of ER/SR (SERCA pumps)
- Na+/Ca2+ exchangers extrude Ca2+ out across plasma membrane or from mitochondria into cytoplasm.
NCX exchanges {3 Na+}:{1 Ca2+}, deriving energy from
Na+ gradient.
Cytoplasmic buffers restrict the ______ and create _____
spatial spread of Ca2+
distinct signaling domains
Effectors
- Surface Membrane Potential
- Protein Kinase C
- Synaptotagmin
- Calmodulin (multiple downstream targets)
Surface Membrane Potential
Ca2+ channels, Ca2+-activated channels
(Neuronal bursting, cardiac pacemaking)
Protein Kinase C
(Translocation to the membrane)
Synaptotagmin
(Ca2+-dependent fusion of synaptic vesicles)
Calmodulin
(multiple downstream targets)
Binding of Ca2+ causes C2 domains to
associate with the plasma membrane
Calmodulin binds to and confers
Ca2+ regulation to a large number of other proteins, including ion channels, protein kinases and phosphatases, and cyclic nucleotide phosphodiesterases.
The EF-hand motif of calmodulin is found in
many other Ca2+ effectors, including parvalbumin (a cellular Ca2+ buffer), calpain (a Ca2+-activated protease) and troponin.
There are also many Ca2+-binding motifs that
do not resemble C2 domains or EF hands.
sources of calcium:
- ER/SR
- extra cellular
- nuclear envelope
- mitochondria
Transporters calcium Movements are much _____than via ion channels
slower
Na+/Ca2+ exchangers (NCX, RetX) function:
extrude Ca2+ out across plasma membrane or from mitochondria into cytoplasm. NCX exchanges {3 Na+}:{1 Ca2+}, deriving energy from Na+ gradient.
The cytoplasmic buffers (e.g., parvalbumin) restrict the _______
spatial and temporal spread of Ca2+.
The cytoplasmic buffers serve as a ______
temporary storage site for Ca2+ while the relatively slow transport processes are operating.
effectors: (4)
An effector is how calcium does something:
- surface membrane potential
- protein kinase C
- synaptotagmin
- Calmodulin
Effector: surface membrane potential
can do this directly:
Ca2+ channels,
Also hyper polarized: Ca2+-activated channels
(Neuronal bursting, cardiac pacemaking)
Effector: Protein Kinase C
Activated by calcium or diacylglycerol
Translocation to the membrane
Effector: Synaototagmin
Ca2+ dependent fusion of synaptic vesicles
Binding of Ca2+ causes C2 domains to
associate with the plasma membrane
