| Structural highlights
Function
[RTN3_HUMAN] May be involved in membrane trafficking in the early secretory pathway. Inhibits BACE1 activity and amyloid precursor protein processing. May induce caspase-8 cascade and apoptosis. May favor BCL2 translocation to the mitochondria upon endoplasmic reticulum stress. In case of enteroviruses infection, RTN3 may be involved in the viral replication or pathogenesis. Induces the formation of endoplasmic reticulum tubules (PubMed:25612671).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The endoplasmic reticulum (ER) is selectively degraded by autophagy (ER-phagy) through proteins called ER-phagy receptors. In Saccharomyces cerevisiae, Atg40 acts as an ER-phagy receptor to sequester ER fragments into autophagosomes by binding Atg8 on forming autophagosomal membranes. During ER-phagy, parts of the ER are morphologically rearranged, fragmented, and loaded into autophagosomes, but the mechanism remains poorly understood. Here we find that Atg40 molecules assemble in the ER membrane concurrently with autophagosome formation via multivalent interaction with Atg8. Atg8-mediated super-assembly of Atg40 generates highly-curved ER regions, depending on its reticulon-like domain, and supports packing of these regions into autophagosomes. Moreover, tight binding of Atg40 to Atg8 is achieved by a short helix C-terminal to the Atg8-family interacting motif, and this feature is also observed for mammalian ER-phagy receptors. Thus, this study significantly advances our understanding of the mechanisms of ER-phagy and also provides insights into organelle fragmentation in selective autophagy of other organelles.
Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes.,Mochida K, Yamasaki A, Matoba K, Kirisako H, Noda NN, Nakatogawa H Nat Commun. 2020 Jul 3;11(1):3306. doi: 10.1038/s41467-020-17163-y. PMID:32620754[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ He W, Lu Y, Qahwash I, Hu XY, Chang A, Yan R. Reticulon family members modulate BACE1 activity and amyloid-beta peptide generation. Nat Med. 2004 Sep;10(9):959-65. Epub 2004 Aug 1. PMID:15286784 doi:http://dx.doi.org/10.1038/nm1088
- ↑ Wakana Y, Koyama S, Nakajima K, Hatsuzawa K, Nagahama M, Tani K, Hauri HP, Melancon P, Tagaya M. Reticulon 3 is involved in membrane trafficking between the endoplasmic reticulum and Golgi. Biochem Biophys Res Commun. 2005 Sep 9;334(4):1198-205. PMID:16054885 doi:http://dx.doi.org/S0006-291X(05)01471-3
- ↑ Xiang R, Liu Y, Zhu L, Dong W, Qi Y. Adaptor FADD is recruited by RTN3/HAP in ER-bound signaling complexes. Apoptosis. 2006 Nov;11(11):1923-32. doi: 10.1007/s10495-006-0082-0. PMID:17031492 doi:http://dx.doi.org/10.1007/s10495-006-0082-0
- ↑ Wan Q, Kuang E, Dong W, Zhou S, Xu H, Qi Y, Liu Y. Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to endoplasmic reticulum stress. Apoptosis. 2007 Feb;12(2):319-28. PMID:17191123 doi:http://dx.doi.org/10.1007/s10495-006-0574-y
- ↑ Urade T, Yamamoto Y, Zhang X, Ku Y, Sakisaka T. Identification and characterization of TMEM33 as a reticulon-binding protein. Kobe J Med Sci. 2014 Nov 6;60(3):E57-65. PMID:25612671
- ↑ Mochida K, Yamasaki A, Matoba K, Kirisako H, Noda NN, Nakatogawa H. Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes. Nat Commun. 2020 Jul 3;11(1):3306. doi: 10.1038/s41467-020-17163-y. PMID:32620754 doi:http://dx.doi.org/10.1038/s41467-020-17163-y
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