Premium
Connexin/gap junctions and cytoskeletons synergistically control lens fiber cell morphogenesis and metabolism
Author(s) -
Gong Xiaohua,
Li Rachel,
Xia Chun-hong
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.07158
Subject(s) - microbiology and biotechnology , cytoskeleton , actin , lens fiber , gap junction , morphogenesis , actin cytoskeleton , chemistry , lens (geology) , biophysics , cell , biology , biochemistry , nucleus , intracellular , gene , paleontology
We have investigated the underlying mechanisms for how a loss of the Gja3 gene (encoding Cx46) leads to variable nuclear cataracts between the C57BL/6J (B6), 129SvJae (129) and B6/129 strain backgrounds, and determined how the genetic variances of periaxin (encoding a cytoskeletal scaffold protein) and CP49 (encoding an intermediate filament protein) modulate the cataract formation. We hypothesize that the Cx46 gap junctions and cytoskeletons synergistically support lens transparency by not only controlling the fiber cell morphogenesis during development but also regulating the exchanges of metabolites between fiber cells to maintain lens homeostasis. Using genetic manipulation and confocal imaging analysis, we have found that both B6‐CP49 and B6‐periaxin inhibit the severity of nuclear cataracts and that the 129‐periaxin proteins are predominantly colocalized with F‐actin and associated with abnormal protrusions on fiber cell surface. The degree of disrupted inner fiber cell surface topology is correlated with the severity of nuclear cataract formation. Metabolite profiling has revealed changes of antioxidants, glycolysis pathway intermediates and lipids compositions in Gja3 knockout (KO) lenses of different strain backgrounds. The Gja3 KO lenses have significant lower levels of glutathione (GSH) than wild‐type controls. Combined effects of gap junctions, CP49‐intermediate filament and periaxin‐mediated cytoskeleton synergistically regulate the interdigitation structures and metabolism of lens inner fiber cells, which modulate lens transparency, homeostasis and cataractogenesis. Support or Funding Information Supported by EY013849 grant from the National Eye Institute