Malformation of junctional microdomains in cataract lens membranes from a type II diabetes patient.
In eye core lens membranes, aquaporin-0 (AQP0) and connexins (Cx) form together well-structured supramolecular assemblies, the junctional microdomains, in which they assure water, ion, metabolite, and waste transport. Additionally, they mediate cell-cell adhesion-forming thin junctions (AQP0) and gap junctions (Cx). We have used atomic force microscopy and biochemical methods to analyze and compare the structure of junctional microdomains in human cataract lens membranes from a type II diabetes patient and healthy lens membranes from calf. A healthy intercellular junctional microdomain consists in average of approximately 150 tetragonally arranged (a = b = 65.5 A, gamma = 90 degrees) AQP0 tetramers surrounded by densely packed non-ordered connexon channels. Gap-junction connexons act as lineactants inside the membrane and confine AQP0 in the junctional microdomains. In the diabetic cataract lens, connexons were degraded, and AQP0 arrays are malformed. We conceptualize that absence of connexons lead to breakdown of cell nutrition.
Mangenot
Stéphanie
S
Institut Curie, Equipe INSERM Avenir, UMR168-CNRS, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.
Buzhynskyy
Nikolay
N
Girmens
Jean-François
JF
Scheuring
Simon
S
D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D020346:Aquaporins / Q000737:chemistry / Q000378:metabolism; D002386:Cataract / Q000378:metabolism*; D002417:Cattle; D017630:Connexins / Q000737:chemistry / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism* / Q000648:ultrastructure; D018625:Microscopy, Atomic Force
D020346:Aquaporins; D017630:Connexins; D005136:Eye Proteins; C030328:aquaporin 0