Page 28 - F. Cell biology

[F. Cell biology-18]

NCLLR regulates non-autophagic LC3 lipidation on the Golgi

apparatus through ATG16L1 recruitment

Jaemin Kang¹, Cathena Meiling Li¹, DoHyeong Na¹, Yong-Keun Jung¹˙*

¹School of Biological Sciences, Seoul National Univesity, Seoul 08826, Korea

Autophagy mediates lysosomal degradation of intracellular cargos via autophagy-related (ATG) proteins. Emerging
evidences suggest that ATG proteins also have autophagy-independent functions in various biological processes.
ATG8/LC3 lipidation not only regulates autophagy but also participates in endocytosis, phagocytosis and

extracellular vesicle secretion. Although recent reports showed that LC3 lipidation occurs on the Golgi apparatus

following Golgi damages and chemical damages, its molecular mechanism and biological function remain largely
unknown. Here, we demonstrate that NCLLR overexpression induces significant accumulation of lipidated LC3 on
the Golgi apparatus via ATG5-dependent manner. We found that NCLLR interacted with ATG16L1, and the coiled-

coil domain and WD40 repeat of ATG16L1 was required for its recruitment to the Golgi apparatus. With the assays
employing DQ-Red BSA and tandem mCherry-GFP-LC3, we observed that the NCLLR-induced LC3 clusters did not

fuse with acidic lysosome compartments. Surprisingly, V-type ATPase inhibitors, but not chloroquine, inhibited LC3
accumulation by NCLLR. Together, these results suggest that NCLLR regulates non-autophagic LC3 lipidation on the

Golgi apparatus through interaction with ATG16L1 and in a V-type ATPase-dependent manner