Phosphoinositides and PLC

Question 1

Where can phosphatidylinositol be phosphorylated?

Answer 1

On 3;Oh, 4’OH or 5’OH

Question 2

Are phosphoinositides structural lipids?

Answer 2

No

Question 3

What are the functions of phosphoinositides?

Answer 3

• Regulators of integral membrane proteins (e.g. open/close channels)
• act as membrane localised sites for recruitment of cytosolic proteins
• Substrates for Pi-PLC

Question 4

What is produced by the reaction between PIP2 and PI-PLC?

Answer 4

• DAG
• Ins (1,4,5) P3

Question 5

Once produced by PI-PLC what does DAG do?

Answer 5

Stays in cytosolic leaflet of plasma membrane and does on the regulate through PKC cascade

Question 6

Once produce by PI-PLC what does Ins(1,4,5)P3 do?

Answer 6

Rapdily diffuses throughout cytoplasm

Question 7

What is the structure of PI-PLC enzymes?

Answer 7

• Catalytic centre comprised of domains X and Y come together to produce the PLC activity which drives hydrolysis

Question 8

What else can affect the particular modulation of PI-PLC?

Answer 8

Additional nuclear domains

Question 9

What is the function of PLCβ?

Answer 9

Recruited to cytoplasmic leaflet of plasma membrane and leads to hydrolysis of PIP2 and diffusion of IP3 through cystsol

Question 10

What is the structure of PLCγ?

Answer 10

Contains a modular domain inserted into catalytic domain

Question 11

How is PLCγ recruited from cytosol?

Answer 11

• EGF dimerises and auto-phosphorylates tyrosines
• These act as docking sites for proteins which contain SH2 domains (like PLCγ)

Question 12

Where is PLCγ recruited to?

Answer 12

Activated EGF receptor

Question 13

How is intracellular free Ca²⁺ kept low?

Answer 13

Either through extruding it or pumpong it into intracellular stores

Question 14

What modulates the storage of Ca2+ in the ER?

Answer 14

IP3

Question 15

How does IP3 modulate Ca²⁺ stores in ER

Answer 15

• Binds to IP3 receptor present on ER which is a Ca²⁺ channel
• Causes channel to open and Ca²⁺ flows out into cytoplasm