July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
JCAD (Junctional Protein Associated with Coronary Artery Disease) is a prominent cell-cell junction protein in the trabecular meshwork
Author Affiliations & Notes
  • Philip Mzyk
    Duke University, Durham, North Carolina, United States
  • Rupalatha Maddala
    Duke University, Durham, North Carolina, United States
  • Vasanth Rao
    Duke University, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Philip Mzyk, None; Rupalatha Maddala, None; Vasanth Rao, None
  • Footnotes
    Support  NIH Grants R01 EY018590 and R01 EY028823
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5126. doi:
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      Philip Mzyk, Rupalatha Maddala, Vasanth Rao; JCAD (Junctional Protein Associated with Coronary Artery Disease) is a prominent cell-cell junction protein in the trabecular meshwork. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5126.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Aqueous humor (AH) drainage through the paracellular routes (intercellular space between the cells) of the trabecular pathway is considered to be important for the homeostasis of intraocular pressure. However, the nature of cell-cell junctions in the trabecular pathway is not well defined. In this study, we characterized for the first time, the expression and distribution of JCAD, a newly identified endothelial cell-cell junctional protein which is abundant in trabecular meshwork cells.

Methods : Human trabecular meshwork (TM) adhesome (components of cell-matrix complexes) protein fraction was subjected to phosphoaffinity pulldown assay and the phospho-specific proteins were identified by mass spectrometry. JCAD, one of the phospho proteins identified from the adhesome fraction was further characterized for its distribution, colocalization and regulation in trabecular meshwork cells and the trabecular pathway by immunoblot, immunofluorescence, and siRNA approaches.

Results : JCAD, whose mutation is associated with coronary artery disease and late onset Alzheimer disease, was found to be one of the prominent tyrosine-phosphorylated proteins of the human TM cell adhesome based on three biological repeats. JCAD is easily detectable in the lysates of human TM cells by immunoblot analysis, shows a doublet of ~150-160 kDa and distributes relatively intensely to the membrane fraction compared to the soluble fraction. In human TM cells, JCAD distributes discretely and intensely to the cell-cell junctions and colocalizes with N-cadherin, β-catenin and αE-catenin. JCAD expression is induced by RhoA activation in human TM cells and its deficiency by siRNA affects cell-cell attachment. JCAD is confirmed to be expressing in both TM and SC of the human conventional AH drainage pathway based on immunofluorescence.

Conclusions : This ongoing study reports the expression and distribution of the newly characterized endothelial cell-cell junctional protein JCAD in human TM cells. JCAD is highly tyrosine-phosphorylated and colocalizes with N-cadherin, indicating its potential role in AH outflow and permeability. These findings warrant further study to explore JCAD’s role in the homeostasis of IOP.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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