Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy

Paolo Grumati, Giulio Morozzi, Soraya Hölper, Muriel Mari, Marie-Lena I. E. Harwardt, Riqiang Yan, Stefan Müller, Fulvio Reggiori, Mike Heilemann, Ivan Dikic*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

217 Citaten (Scopus)
437 Downloads (Pure)

Samenvatting

The turnover of endoplasmic reticulum (ER) ensures the correct biological activity of its distinct domains. In mammalian cells, the ER is degraded via a selective autophagy pathway (ER-phagy), mediated by two specific receptors: FAM134B, responsible for the turnover of ER sheets and SEC62 that regulates ER recovery following stress. Here, we identified reticulon 3 (RTN3) as a specific receptor for the degradation of ER tubules. Oligomerization of the long isoform of RTN3 is sufficient to trigger fragmentation of ER tubules. The long N-terminal region of RTN3 contains several newly identified LC3-interacting regions (LIR). Binding to LC3s/GABARAPs is essential for the fragmentation of ER tubules and their delivery to lysosomes. RTN3-mediated ER-phagy requires conventional autophagy components, but is independent of FAM134B. None of the other reticulon family members have the ability to induce fragmentation of ER tubules during starvation. Therefore, we assign a unique function to RTN3 during autophagy.

Originele taal-2English
Artikelnummer25555
Aantal pagina's32
TijdschrifteLife
Volume6
DOI's
StatusPublished - 15-jun.-2017

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