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Kidney Week

Abstract: PO0159

Protein Deacetylase SIRT2 Regulates Exosome Release of GPRC5B for Epithelial Tubule Growth

Session Information

  • AKI Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Author

  • Kwon, Sang-Ho, Augusta University, Augusta, Georgia, United States
Background

Exosomes, small membrane vesicles, are formed intracellularly within multivesicular bodies (MVBs) and are released extracellularly upon fusion with the plasma membrane. Previously we have shown that exosomal release of GPRC5B, an orphan G protein-coupled receptor (GPCR) promotes epithelial tubule growth, and the L-type lectin LMAN2 limits trans-Golgi Network-to-endosomes traffic of GPRC5B.

Methods

Using mass spectrometry, CRISPR/Cas9 genetic manipulation, and imaging, we studied how LMAN2 regulates exosomal release of GPRC5B.

Results

Here, we report the protein deacetylase sirtuin 2 (SIRT2) as a novel interactor of LMAN2. Loss of SIRT2 expression resulted in exosomal release of LMAN2, a Golgi resident protein, together with increased exosomal release of GPRC5B. Furthermore, loss of SIRT2 increased total number of extracellular vesicles (EVs) including exosomes, indicating increased MVB-to-EV flux. While knockout of SIRT1 increased EV release with enlarged late endolysosome, knockout of SIRT2 did not exhibit endolysosome enlargement for increased EV release.

Conclusion

Taken together, our study suggests that SIRT2 regulates cargo loading to MVBs and MVB-to-EV flux through a mechanism distinct from that of SIRT1.

Funding

  • NIDDK Support