Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation (Morita et al., J Cell Biol)
2018.08.09 Recent Publications
Keigo Morita, Yutaro Hama, Tamaki Izume, Norito Tamura, Toshihide Ueno, Yoshihiro Yamashita, Yuriko Sakamaki, Kaito Mimura, Hideaki Morishita, Wataru Shihoya, Osamu Nureki, Hiroyuki Mano, and Noboru Mizushima
Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation
J Cell Biol, 2018, August 9 DOI: 10.1083/jcb.201804132
Macroautophagy is an intracellular degradation process that requires multiple autophagy-related (ATG) genes. In this study, we performed a genome-wide screen using the autophagic flux reporter GFP-LC3-RFP and identified TMEM41B as a novel ATG gene. TMEM41B is a multispanning membrane protein localized in the endoplasmic reticulum (ER). It has a conserved domain also found in vacuole membrane protein 1 (VMP1), another ER multispanning membrane protein essential for autophagy, yeast Tvp38, and the bacterial DedA family of putative half-transporters. Deletion of TMEM41B blocked the formation of autophagosomes at an early step, causing accumulation of ATG proteins and small vesicles but not elongating autophagosome-like structures. Furthermore, lipid droplets accumulated in TMEM41B-knockout (KO) cells. The phenotype of TMEM41B-KO cells resembled those of VMP1-KO cells. Indeed, TMEM41B and VMP1 formed a complex in vivo and in vitro, and overexpression of VMP1 restored autophagic flux in TMEM41B-KO cells. These results suggest that TMEM41B and VMP1 function together at an early step of autophagosome formation.