Distinct role of Sirtuin 1 (SIRT1) and Sirtuin 2 (SIRT2) in inhibiting cargo-loading and release of extracellular vesicles.

Scientific reports (2019-12-29)
Byung Rho Lee, Bethany J Sanstrum, Yutao Liu, Sang-Ho Kwon
ABSTRAKT

Exosomes, vehicles for intercellular communication, are formed intracellularly within multivesicular bodies (MVBs) and are released upon fusion with the plasma membrane. For their biogenesis, proper cargo loading to exosomes and vesicle traffic for extracellular release are required. Previously we showed that the L-type lectin, LMAN2, limits trans-Golgi Network (TGN)-to-endosomes traffic of GPRC5B, an exosome cargo protein, for exosome release. Here, we identified that 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, along with increased exosomal release of GPRC5B. Furthermore, knockout of SIRT2 increased total number of extracellular vesicles (EVs), 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. 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.

MATERIAŁY
Numer produktu
Marka
Opis produktu

Sigma-Aldrich
MISSION® pLKO.1-puro Empty Vector Control Plasmid DNA, Contains no shRNA insert
Sigma-Aldrich
ANTI-FLAG® antibody, Rat monoclonal, clone 6F7, purified from hybridoma cell culture
Sigma-Aldrich
Anti-GAPDH Antibody, from chicken, purified by affinity chromatography
Sigma-Aldrich
Anti-ACTIN antibody produced in rabbit, affinity isolated antibody