10. Orai1-STIM1 and SOCE

Question 1

Ca2+ is an important 2nd messenger in lymphocytes and is essential in regulating various intracellular pathways that control critical cell functions
TRUE OR FALSE

Answer 1

TRUE

Question 2

BLANK stimulates IP3 receptors in the membrane of the ER to allow BLANK release from BLANK

Answer 2

IP3 stimulates IP3 receptors in the membrane of the ER to allow Ca2+ release from intracellular stores.

Question 3

Small number of Ca2+ channels opened =

More Ca2+ channels opened =

Answer 3

Ca2+ release not sufficient to feedback and activate adjacent channels. Ca2+ release reversed by SERCA channels.

Ca2+ feedback able to increase channel activation.

“Blip” “Puff” “Wave”

Question 4

Ca2+ Signalling Cascade:

Answer 4

The Ca2+ signalling cascade is commonly initiated by the stimulation of the TCR or BCR, resulting in Ca2+ release from intracellular stores to the cytoplasm.

After depletion from intracellular stores, Ca2+ enters the cell from the extracellular space through Ca2+ channels in the plasma membrane.

Ca2+ can then bind to the cytoplasmic adaptor “Calmodulin”, which forms a complex with “Calcineurin”, resulting in the dephosphorylation and nuclear translocation of NFAT proteins.

The Ca2+-Calmodulin complex can also activate the transcription factor CREB via Ca2+/Calmodulin-dependent protein kinase II (CaMKII), as well as myocyte enhancer factor 2 (MEF2) and NF-kB

These transcription factors then induce gene transcription involved in cell proliferation, cytokine production, survival, and cell death.

Question 5

Release of Ca2+ from intracellular stores elicits Ca2+ entry through plasma membrane BLANKS

Answer 5

Release of Ca2+ from intracellular stores elicits Ca2+ entry through plasma membrane Ca2+ release-activated Ca2+ (CRAC) channels:

Question 6

BLANK and BLANK have been implicated in mediating the CRAC current.

Answer 6

Stromal Interaction Molecule (STIM1) and Orai1 have been implicated in mediating the CRAC current.

Question 7

CRAC channel is composed of 2 components that act together:

Answer 7

Orai1: The pore-forming subunit. Found in the plasma membrane.

STIM1: The regulatory subunit. Located in the ER membrane.

Question 8

Orai1 monitors Ca2+ levels in the ER.

TRUE OR FALSE

Answer 8

FALSE

STIM1 monitors Ca2+ levels in the ER.

Question 9

Ca2+-bound STIM1 are grouped up on the ER membrane

Answer 9

FALSE

Ca2+-bound STIM1 are spread out across the ER membrane

Question 10

During low Ca2+ levels, the STIM1 proteins oligomerise/group-up in close-proximity to the plasma membrane so that STIM1 can interact with and activate Orai1
TRUE OR FALSE

Answer 10

TRUE
This triggers a Ca2+ influx from the extracellular space to the ER. This process is termed store-operated Ca2+-entry (SOCE).