Zinc Signalling

Question 1

How can zinc become released from metallothionein?

Answer 1

Nitrosylation or thiol ligand oxidation of MT.

Question 2

What evidence has linked NO to Zn release from MT?

Answer 2

Bernal et al (2009)

• Arterioles in lung - cells treated with hypoxia –> Zn release from MT.
• Add iNOS inhibitor - no Zn release.
• Make MT deficient - less Zn release.

Question 3

How do we know ZnT5 is important in mast cells?

Answer 3

ZnT5 KO mice –> defects in mast cell delayed type allergic reactions perhaps due to FcERI induced translocation of PKC to PM and translocation of NK-kB to nucleus becoming impaired.

Question 4

How is ZIP6 implicated in breast cancer?

Answer 4

E-cadherin downregulation is a hallmark of EMT.

ZIP6 expressing breast cancer cells have downregulated E-cadherin associated with cell migration and metastatsis.

Question 5

How is ZIP8 linked to immunity?

Answer 5

Lets zinc into cell.
Zinc binds specific binding site on catalytic domain of IKK-B - IKK-B can no longer phosphorylate IK-b - NFkB not translocated and recution in pro-inflammatory genes and therefore cold symptoms.

Question 6

What is the phenotype of ZIP14 KOs?

Answer 6

Zn inhibition of PDE –> less GPCR inhibition –> more CREB –> retarded growth and impaired gluconeogenesis.

Question 7

How are SMADs affected by zinc?

Answer 7

All have a zinc binding motif.

Zn2+ activates SMAD localisation to nucleus when released by Zip13.

Question 8

What is the phenotype of Zip13 KOs?

Answer 8

disorganised hard and connective tissues e.g. bone, skin, teeth as affects fate of stem cells becoming cartilage cells.