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Cited by 219

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Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation

Open access
Morita, Keigo, Hama, Yutaro, Izume, Tamaki, Tamura, Norito, Ueno, Toshihide, Yamashita, Yoshihiro, Sakamaki, Yuriko, Mimura, Kaito, Morishita, Hideaki, Shihoya, Wataru, Nureki, Osamu, Mano, Hiroyuki, Mizushima, Noboru·2018·Journal of Cell Biology

Abstract

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.

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Metadata

Authors
Morita, K., Hama, Y., Izume, T., Tamura, N., Ueno, T., Yamashita, Y., Sakamaki, Y., Mimura, K., Morishita, H., Shihoya, W., Nureki, O., Mano, H., & Mizushima, N.
Venue
Journal of Cell Biology
Published
2018-08-09
Volume
217
Issue
11
Pages
3817-3828
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2887384294
Cited by
219
References
7
FWCI
14.66
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation. https://app.cochat.ai/papers/10.1083/jcb.201804132
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Morita, K., Hama, Y., Izume, T., Tamura, N., Ueno, T., Yamashita, Y., Sakamaki, Y., Mimura, K., Morishita, H., Shihoya, W., Nureki, O., Mano, H., & Mizushima, N. (2018). Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome formation. Journal of Cell Biology. https://doi.org/10.1083/jcb.201804132

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