%0 Journal Article
%T Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation
%A Hama
%A Hideaki
%A Hideaki Morishita
%A Hiroyuki
%A Hiroyuki Mano
%A Izume
%A Kaito
%A Kaito Mimura
%A Keigo
%A Keigo Morita
%A Mano
%A Mimura
%A Mizushima
%A Morishita
%A Morita
%A Noboru
%A Noboru Mizushima
%A Norito
%A Norito Tamura
%A Nureki
%A Osamu
%A Osamu Nureki
%A Sakamaki
%A Shihoya
%A Tamaki
%A Tamaki Izume
%A Tamura
%A Toshihide
%A Toshihide Ueno
%A Ueno
%A Wataru
%A Wataru Shihoya
%A Yamashita
%A Yoshihiro
%A Yoshihiro Yamashita
%A Yuriko
%A Yuriko Sakamaki
%A Yutaro
%A Yutaro Hama
%J JCB | The Journal of Cell Biology
%D 2018
%R 10.1083/jcb.201804132
%X 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.
%U http://jcb.rupress.org/content/217/11/3817