Identification of Protein-Protein Interactors of the Corneal Dystrophy-Causing Protein, SLC4A11

• Author / Creator

  ALSHUMAIMERI, NADA A.

• Endothelial corneal dystrophies are eye diseases characterized by dysfunction of the innermost layer of the cornea, resulting in disruption of the regulation and homeostasis of corneal deturgescence and, ultimately, impaired visual acuity. Gene mutations are responsible for many corneal endothelial dystrophies, suggesting that further insight into the roles of these genes and how their coded proteins interact with others may provide us with a better understanding of the causes behind these disorders. Mutations of the solute carrier family 4-member 11 (SLC4A11), a member of the SLC4 family of bicarbonate transporters, cause congenital hereditary endothelial dystrophy (CHED) and some cases of Fuchs endothelial corneal dystrophy (FECD). SLC4A11 is not, however, a bicarbonate transporter. Rather SLC4A11 is a H+/ OH-, H2O, and NH3 transporter. SLC4A11 mutations compromise the trans-endothelial water flux of the cornea. This arises from misfolding of SLC4A11 protein, causing its retention in the endoplasmic reticulum (ER), or affecting the function of SLC4A11. SLC4A11 also plays a role in corneal endothelial cell (CEC) adhesion to the underlying Descemet’s membrane as well, suggesting that defective CEC adhesion may contribute to the pathophysiology of endothelial dystrophies. This thesis investigates the role of SLC4A11 in endothelial corneal dystrophies by identification of protein-protein interactors of SLC4A11, using the membrane yeast two hybrid system (MYTH). Six unique, full-length proteins were detected as protein interactors with SLC4A11, and one of them, Ovarian Cancer Immunoreactive Antigen Domain Containing-1 (OCIAD1), was studied in greater detail using a variety of cell and tissue models due to its role in both the mitochondria and cell adhesion processes. Here, we show clear colocalization of SLC4A11 with OCIAD1 in bovine corneas, and that co-expression of the two proteins increases cell adhesion to the cornea Descemet’s membrane and protein migration to the cell surface in HEK293 cells. This thesis describes the identification of protein-protein interaction between OCIAD1 and SLC4A11.

• Subjects / Keywords

  • SLC4A11
  • MYTH
  • OCIAD1
  • Endothelial corneal dystrophies
  • Protein-Protein Interaction

• Graduation date

  Spring 2022

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-c8df-0y51

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.