L11 - IP3 and calcium release

Question 1

name the molecule that binds to the ER to cause calcium release

Answer 1

IP3

Question 2

why is the calcium release not continous but in ‘bursts’ or ‘oscillations’

Answer 2

feedback loops

positive feedback loop:
low Ca2+ levels enhance IP3 receptor opening –> more calcium released

negative feedback:
high Ca2+ inhibit receptor –> temporaily stop further release

= balance between the 2 loops leads to oscilatory Ca2+ signals

Question 3

why is calcium oscialltion important

Question 4

what is SOCE and why is it needed

Answer 4

store operated calcium entry

= to sustain long-term Ca2+ signalling -> cell must replinish ER Ca2+

Question 5

describe the mechansism of SOCE (store operated calcium entry)

Answer 5

1. Ca2+ level drop in ER -> STIM1 ER membrane protein activated
2. STIM1 changes shape + migrates to area in ER close to plasmam membrane
3. STIM1 actiavtes Orai1 on plasmam membrabe

= refills ER directly from OUTSIDE the cell
= maintains cytosolic Ca2+ for ongoing signalliung while this happens

Question 6

what is Calmodulin-dependant protein kinase 2 (CaMK2)

Answer 6

kinase with multiple subunits

Senses Ca2+ oscillation patterns to produce specific responses

= bound by Ca2+ to be activated

Question 7

describe activation of CaMK2 (calmodulin-dependant protein kinase 2)

Answer 7

binding of Ca2+ to CaMK2 activates complex

Repeated spikes/oscilations = CaMK2 increasingly activated due to autophosphorylation:

–> CaMK2 stays active even after Ca2+ levels drop

Question 8

describe how CaMK2 decodes oscillations to cause downstream affects

Answer 8

low frequency Ca2+ spikes = not enough to sustain activaction

1. High frequency Ca2+ spikes = maintain CaMK2 in active state
2. triggers downstream pathways:
   - gene transcription
   - cell cycle progression
   - memory formation in neurons