Exosomal GAPDH from Proximal Tubule Cells Regulate ENaC Activity
Kishore Kumar Jella1, Ling Yu2, Qiang Yue3
1Department of Radiation Oncology, Emory University School of Medicine, Atlanta, Georgia.
Plos One
|November 2, 2016
Summary
Exosomes from proximal tubule cells regulate epithelial sodium channels (ENaC) in distal tubule cells. This intercellular communication involves GAPDH within exosomes, suggesting a novel regulatory pathway.
Area of Science:
- Cell Biology
- Renal Physiology
- Nanomedicine
Background:
- Exosomes mediate intercellular communication by transferring molecular cargo.
- Epithelial sodium channels (ENaC) are crucial for sodium reabsorption in the kidney.
- Proximal tubule cells communicate with distal tubule and collecting duct cells.
Purpose of the Study:
- To investigate the role of proximal tubule-derived exosomes in regulating ENaC activity in distal tubule cells.
- To identify the molecular mechanisms underlying exosome-mediated regulation of ENaC.
Main Methods:
- Isolation and labeling of exosomes from LLC-PK1 proximal tubule cells.
- Uptake visualization using fluorescent dyes (PKH26) and cell staining (CTX).
- Single-channel patch clamp recordings to assess ENaC open probability.
- Identification of exosomal proteins (GAPDH) and functional assays with inhibitors.
Main Results:
- Exosomes from proximal tubules reduced ENaC open probability in distal tubule cells.
- Active glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was found in proximal tubule exosomes.
- Inhibition of GAPDH activity blunted the exosome-induced effect on ENaC.
- GAPDH and ENaC subunits were shown to associate in kidney cells.
Conclusions:
- Proximal tubule exosomes can regulate ENaC activity in distal tubule cells.
- GAPDH within exosomes plays a role in this communication pathway.
- This study reveals a novel mechanism of intercellular communication in the kidney involving exosomes.
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