| First Author | Foronda H | Year | 2023 |
| Journal | Nature | Volume | 618 |
| Issue | 7964 | Pages | 402-410 |
| PubMed ID | 37225994 | Mgi Jnum | J:337921 |
| Mgi Id | MGI:7506713 | Doi | 10.1038/s41586-023-06090-9 |
| Citation | Foronda H, et al. (2023) Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy. Nature 618(7964):402-410 |
| abstractText | Membrane-shaping proteins characterized by reticulon homology domains play an important part in the dynamic remodelling of the endoplasmic reticulum (ER). An example of such a protein is FAM134B, which can bind LC3 proteins and mediate the degradation of ER sheets through selective autophagy (ER-phagy)(1). Mutations in FAM134B result in a neurodegenerative disorder in humans that mainly affects sensory and autonomic neurons(2). Here we report that ARL6IP1, another ER-shaping protein that contains a reticulon homology domain and is associated with sensory loss(3), interacts with FAM134B and participates in the formation of heteromeric multi-protein clusters required for ER-phagy. Moreover, ubiquitination of ARL6IP1 promotes this process. Accordingly, disruption of Arl6ip1 in mice causes an expansion of ER sheets in sensory neurons that degenerate over time. Primary cells obtained from Arl6ip1-deficient mice or from patients display incomplete budding of ER membranes and severe impairment of ER-phagy flux. Therefore, we propose that the clustering of ubiquitinated ER-shaping proteins facilitates the dynamic remodelling of the ER during ER-phagy and is important for neuronal maintenance. |
