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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 26

Module 2: Figure Ca 2 + signalling toolkit

CNGA1-4 PLC 1-4
CNGB1 AMPAR G q PLC 1-2
(GluR2)
CNGB3 nAChR G 11 PLC 1-4
TRPA1 5-HT3 Agonists G 14 PLC
TRPC1 NMDAR G 15 PLC 1-2
TRPC3-7 (NR1-NR3) Ca 1.1-1.4 GPCRs G PLC PTKRs
V
TRPM2-3 P2X1-7 + Ca 2.1-2.3
V
TRPM7-8 Ca 3.1-3.3 Orai1
V
TRPP2 Ca 1.1 Orai2
V
Adiponectin
+
STIM1
RYR1
Acidic Ca 2+ STIM2 Ca 2+
AdipoR1/2 stores 2+
Ca
NAADP InsP 3
PMCA1-4
Ca 2+ TPC1 +
TPC2 +
InsP R1-3
3
Ca 2+ NCX1-3 ER buffers
Calsequestrin
+
Na Ca 2+ Calreticulin
+ GRP78
+ + + GRP94
K & Na
Ca 2+ RYR2-3
NCKX1-4
SERCA1-3
+
Na cADPR
Ca 2+
Na/Ca + Cytosolic buffers
Ca CalbindinD-28k
exchanger 2+
Calretinin
Ca 2+ Mitochondrial SPCA1-2 Parvalbumin
calcium
uniporter
+ +
ATP Nucleus
synthesis
MTP ROS +
formation + TRPML1 Chromatin Cell
Apoptosis 2+ 2+ remodelling remodelling
Ca Ca Cell
+ Gene
C2 domain EF-hand transcription proliferation
Exocytosis Annexin 1-13 NCS-1 +
Otoferin CaM Hippocalcin
TnC
+ Protein kinase C Calpains Neurocalcin
RASAL Miro1-2 Recoverin
Endocytosis SynaptotagminI-III S100A1-14 VILIP1-3
S100B GCAP1-3 +
S100C KChIP1-4 + Protein synthesis
+ S100P CaBP1-5 + hVps34/mTOR
MICU1
Excitability and
fluid secretion + + + Metabolism
+ DAG kinase
K IP 3 Kinase
BK, SK,IK & TRESK Signalling crosstalk Cytoskeletal Motility Phopho-
remodelling diesterase
- Phosphorylase
Cl Cyclic AMP NO ROS MAPK PI 3-K Actin Myosin
Na + polymerization Actin
TRPM4/5 Ras
TRPV4-6 AC NOS DUOX
Summary of the major components that contribute to the Ca 2 + signalling signalsome.
There is an extensive Ca 2 + signalling toolkit. The green boxes illustrate the membrane Ca 2 + channels, whereas the red boxes are the pumps and
exchangers that move Ca 2 + either out of the cell or back into the endoplasmic reticulum (ER). The purple boxes represent the buffers located in
the cytoplasm or in the endoplasmic reticulum (ER). To carry out its signalling function, Ca 2 + binds to sensors with C2 or EF-hand domains that
then employ a range of effectors to stimulate cellular processes shown in the yellow boxes. These different components are mixed and matched to
construct various Ca 2 + signalling modules (Module 2: Figure Ca 2 + modules) that are then assembled to produce cell-specific signalsomes.
The other main function of CICR is to set up respectively. It is these unitary events that are used to gen-
intracellular Ca 2 + waves where an elevated level of Ca 2 + erate the regenerative waves that make up global Ca 2 +
in one region of the cell (the initiation site) propagates signals.
throughout the rest of the cytoplasm as a regenerat-
ive Ca 2 + wave. Waves can progress by recruiting either
RYRs or inositol 1,4,5-trisphosphate receptors (InsP 3 Rs) Ca 2 + OFF reactions
(Module 2: Figure Ca 2 + -induced Ca 2 + release). These Cells use a variety of mechanisms to remove Ca 2 + from
Ca 2 + waves are made up of elementary Ca 2 + events such the cytoplasm (Module 2: Figure Ca 2 + signalling dynam-
as the sparks and puffs produced by the RYRs and InsP 3 Rs ics). The introduction of Ca 2 + into the cell during the
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