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Kumar D, Lak B, Suntio T, et al. RTN4B interacting protein FAM134C promotes ER membrane curvature and has a functional role in autophagy. Mol Biol Cell. 2021;32(12):1158-1170doi: 10.1091/mbc.E20-06-0409.
Kumar, D., Lak, B., Suntio, T., Vihinen, H., Belevich, I., Viita, T., Xiaonan, L., Vartiainen, A., Vartiainen, M., Varjosalo, M., & Jokitalo, E. (2021). RTN4B interacting protein FAM134C promotes ER membrane curvature and has a functional role in autophagy. Molecular biology of the cell, 32(12), 1158-1170. https://doi.org/10.1091/mbc.E20-06-0409
Kumar, Darshan, et al. "RTN4B interacting protein FAM134C promotes ER membrane curvature and has a functional role in autophagy." Molecular biology of the cell vol. 32,12 (2021): 1158-1170. doi: https://doi.org/10.1091/mbc.E20-06-0409
Kumar D, Lak B, Suntio T, Vihinen H, Belevich I, Viita T, Xiaonan L, Vartiainen A, Vartiainen M, Varjosalo M, Jokitalo E. RTN4B interacting protein FAM134C promotes ER membrane curvature and has a functional role in autophagy. Mol Biol Cell. 2021 Jun 01;32(12):1158-1170. doi: 10.1091/mbc.E20-06-0409. Epub 2021 Apr 07. PMID: 33826365; PMCID: PMC8351555.
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Mol Biol Cell. 2021 Jun 01;32(12):1158-1170. doi: 10.1091/mbc.E20-06-0409. Epub 2021 Apr 07.

RTN4B interacting protein FAM134C promotes ER membrane curvature and has a functional role in autophagy.

Molecular biology of the cell

Darshan Kumar, Behnam Lak, Taina Suntio, Helena Vihinen, Ilya Belevich, Tiina Viita, Liu Xiaonan, Aki Vartiainen, Maria Vartiainen, Markku Varjosalo, Eija Jokitalo

Affiliations

  1. Cell and Tissue Dynamics Research Program.
  2. Electron Microscopy Unit, and.
  3. Molecular Systems Biology Research Group and Proteomics Unit, Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland.

PMID: 33826365 PMCID: PMC8351555 DOI: 10.1091/mbc.E20-06-0409

Abstract

The endoplasmic reticulum (ER) is composed of a controlled ratio of sheets and tubules, which are maintained by several proteins with multiple functions. Reticulons (RTNs), especially RTN4, and DP1/Yop1p family members are known to induce ER membrane curvature. RTN4B is the main RTN4 isoform expressed in nonneuronal cells. In this study, we identified FAM134C as a RTN4B interacting protein in mammalian, nonneuronal cells. FAM134C localized specifically to the ER tubules and sheet edges. Ultrastructural analysis revealed that overexpression of FAM134C induced the formation of unbranched, long tubules or dense globular structures composed of heavily branched narrow tubules. In both cases, tubules were nonmotile. ER tubulation was dependent on the reticulon homology domain (RHD) close to the N-terminus. FAM134C plays a role in the autophagy pathway as its level elevated significantly upon amino acid starvation but not during ER stress. Moreover, FAM134C depletion reduced the number and size of autophagic structures and the amount of ER as a cargo within autophagic structures under starvation conditions. Dominant-negative expression of FAM134C forms with mutated RHD or LC3 interacting region also led to a reduced number of autophagic structures. Our results suggest that FAM134C provides a link between regulation of ER architecture and ER turnover by promoting ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes.

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