AQP0

Question 1

Cataracts is

Answer 1

Clouding of the lens in the eye which leads to decrease vision

Question 2

Lens cataracts is..

Answer 2

A sig problem throughout the world and responsible for majority of visual impairments in adult humans

Question 3

Cataracts develops due to..

Answer 3

Natural mutations in the lens proteins (congenital cataracts) as well as exposure to oxidative agents and radiations

Question 4

AQP0 performs dual function in the lens fibre cells

Main protein forund there

Answer 4

Water pore

Cell-to-cell adhesion

Question 5

AQP0 provides

Answer 5

Structural integrity through tightly ordered packing of fibre cells
Maintain lenticular architecture and decreases light scattering

Question 6

Kumari et al 2013

Answer 6

R33C mutation produced congenital autosomal dominant cataracts

Question 7

Mutant AQP0-R33C showed..

Answer 7

Proper trafficking and membrane localisation like WT-AQP0

Question 8

Kumari et al 2013 functional studies in xenopus oocytes showed..

Answer 8

No statistical difference in water permeability between AQP0-R33C and WT-AQP0
Cell-to-cell adhesion property of AQP0-R33C was sig reduced (P<0.001)
Shown by cell aggregation and cell-to-cell adhesion assay

Question 9

Kumari et al 2013 assay showed cell-to-cell adhesion was affecting

Answer 9

gap junction coupling

Question 10

Conclusion of Kumari et al 2013

Answer 10

Reduction in cell-to-cell adhesion and development of cataracts suggests that the conserved positive charge of extracellular loop A may play a role in bringing fibre cells closer

Question 11

Varadraj et al 2011

Answer 11

Used KO mice to demonstrate AQP0 role in ocular lens transparency and homeostasis
KO caused disorganisation of fibre cells so shows AQP0 adhesion maintains lenticular architecture

Question 12

Jiang et al

Answer 12

AQP0 enhances gap junctions coupling between lens fibre cells

Question 13

Nakazowa et al 2016

Answer 13

AQP0 can bind to itself via the C-loop extracellular domain
Pro-pro in C-loop
Mutations dont affect permeability but adhesion
Independent dual function of AQP0 important for lens transparency

Question 14

Varadaraj et al., 2008

Answer 14

Deletion mutation modified reading frame
Resulted in addition of premature stop codon
Replacement of distal end of 6th TMD and C-terminal domain
Delta-213-AQP0 resulted in impairment of cell membrane localisation of mutant protein in ER without trafficking to plasma membrane
Cytotoxicity due to accumulation of mutant protein