ERdj8 governs the size of autophagosomes during the formation process

Yamamoto, Yo; Kasai, Ayano; Omori, Hiroko; Takino, Tomoe; Sugihara, Munechika; Umemoto, Tetsuo; Hamasaki, Maho; Hatta, Tomohisa; Natsume, Tohru; Morimoto, Richard I.; Arai, Ritsuko; Waguri, Satoshi; Sato, Miyuki; Sato, Ken; Bar-Nun, Shoshana; Yoshimori, Tamotsu; Noda, Tetsuji; Nagata, Kazuhiro

doi:10.1083/jcb.201903127

Cited by 19 publications

(19 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nine different ERjs reside in the human ER ( Table 1 ) [ 79 , 80 , 81 , 130 , 145 , 146 , 147 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 ]. As the name infers, ERjs are characterized by individual J-domains, which allow interaction with BiP via the bottom of its NBD and, to do so, contain four α-helices (helices I–IV) with a loop region containing a highly conserved tripeptide of histidine, proline, and aspartic acid (HPD motif) located between helices II and III.…”

Section: Gating Of the Sec61 Channel By Bipmentioning

confidence: 99%

“…Only ERj3 through ERj6 appear to be involved in protein folding under physiological as well as ER stress conditions and in ERAD. The other ERjs play more specialized roles in ER protein import (Sec63/ERj2 and ERj1) [ 79 , 80 , 81 , 102 , 143 , 145 , 146 , 147 , 151 ] or ER-phagy (ERj8) [ 234 ]. Thus, there is redundancy also at the level of the ERjs, which may explain the non-lethal phenotype of loss of Sec63 function that is associated with polycystic liver disease (see below).…”

Section: Gating Of the Sec61 Channel By Bipmentioning

confidence: 99%

See 1 more Smart Citation

Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex

Sicking

Lang

Bochen

et al. 2021

Cells

View full text Add to dashboard Cite

The rough endoplasmic reticulum (ER) of nucleated human cells has crucial functions in protein biogenesis, calcium (Ca2+) homeostasis, and signal transduction. Among the roughly one hundred components, which are involved in protein import and protein folding or assembly, two components stand out: The Sec61 complex and BiP. The Sec61 complex in the ER membrane represents the major entry point for precursor polypeptides into the membrane or lumen of the ER and provides a conduit for Ca2+ ions from the ER lumen to the cytosol. The second component, the Hsp70-type molecular chaperone immunoglobulin heavy chain binding protein, short BiP, plays central roles in protein folding and assembly (hence its name), protein import, cellular Ca2+ homeostasis, and various intracellular signal transduction pathways. For the purpose of this review, we focus on these two components, their relevant allosteric effectors and on the question of how their respective functional cycles are linked in order to reconcile the apparently contradictory features of the ER membrane, selective permeability for precursor polypeptides, and impermeability for Ca2+. The key issues are that the Sec61 complex exists in two conformations: An open and a closed state that are in a dynamic equilibrium with each other, and that BiP contributes to its gating in both directions in cooperation with different co-chaperones. While the open Sec61 complex forms an aqueous polypeptide-conducting- and transiently Ca2+-permeable channel, the closed complex is impermeable even to Ca2+. Therefore, we discuss the human hereditary and tumor diseases that are linked to Sec61 channel gating, termed Sec61-channelopathies, as disturbances of selective polypeptide-impermeability and/or aberrant Ca2+-permeability.

show abstract

Section: Gating Of the Sec61 Channel By Bipmentioning

confidence: 99%

Section: Gating Of the Sec61 Channel By Bipmentioning

confidence: 99%

Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex

Sicking

Lang

Bochen

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…The ERdj proteins are a family of proteins harboring the DNAJ domain that cooperate with the molecular chaperones and play diverse roles in the ER [54][55][56]. Recently, we analyzed their uncharacterized member, ERdj8 [12]. ERdj8 was partially colocalized with PIS-enriched ER subdomains and also partially colocalized with Atg proteins (Fig.…”

Section: Main Textmentioning

confidence: 99%

“…The size of autophagosomes varies from a few hundred nanometers in diameter to over a micrometer [ 10 , 11 ]. Recently, we have reported that the ER resident membrane protein, ERdj8/DNAJC16, is involved in the size determination of autophagosomes [ 12 ]. Herein, we introduce recent advances in the relationship between autophagosome formation and endoplasmic reticulum.…”

Section: Introductionmentioning

confidence: 99%

Autophagosome formation in relation to the endoplasmic reticulum

Yamamoto

Noda

2020

J Biomed Sci

Self Cite

View full text Add to dashboard Cite

Autophagy is a process in which a myriad membrane structures called autophagosomes are formed de novo in a single cell, which deliver the engulfed substrates into lysosomes for degradation. The size of the autophagosomes is relatively uniform in non-selective autophagy and variable in selective autophagy. It has been recently established that autophagosome formation occurs near the endoplasmic reticulum (ER). In this review, we have discussed recent advances in the relationship between autophagosome formation and endoplasmic reticulum. Autophagosome formation occurs near the ER subdomain enriched with phospholipid synthesizing enzymes like phosphatidylinositol synthase (PIS)/CDP-diacylglycerol-inositol 3-phosphatidyltransferase (CDIPT) and choline/ethanolamine phosphotransferase 1 (CEPT1). Autophagy-related protein 2 (Atg2), which is involved in autophagosome formation has a lipid transfer capacity and is proposed to directly transfer the lipid molecules from the ER to form autophagosomes. Vacuole membrane protein 1 (VMP1) and transmembrane protein 41b (TMEM41b) are ER membrane proteins that are associated with the formation of the subdomain. Recently, we have reported that an uncharacterized ER membrane protein possessing the DNAJ domain, called ERdj8/DNAJC16, is associated with the regulation of the size of autophagosomes. The localization of ERdj8/DNAJC16 partially overlaps with the PIS-enriched ER subdomain, thereby implying its association with autophagosome size determination.

show abstract

“…This dynamic interaction with unfolded proteins prevents their unfavorable interactions and co-aggregation with other folding intermediates. Nucleotide exchange factors and J-domain containing co-chaperones (ERdj1-8) modulate the activity of BiP and help recruiting clients [7,8]. When a protein fails to fold in the ER, it can be subjected to the ER-associated degradation (ERAD) machinery and degraded via the ubiquitin-proteasome system [9].…”

Section: Introductionmentioning

confidence: 99%

The Unfolded Protein Response as Guardian of the Secretory Pathway

Radanović¹,

Ernst²

2021

Preprint

View full text Add to dashboard Cite

The endoplasmic reticulum (ER) is the major site of membrane biogenesis in most eukaryotic cells. As the entry point to the secretory pathway, it handles more than 10.000 different secretory and membrane proteins. The membrane insertion of proteins, their folding, and ER exit are affected by the lipid composition of the ER membrane and its collective membrane stiffness. The ER is also a hotspot of lipid metabolism for membrane lipids including sterols, glycerophospholipids, ceramides and neural storage lipids. The unfolded protein response (UPR) bears an evolutionary conserved, dual sensitivity to both protein folding-imbalances in the ER lumen and aberrant compositions of the ER membrane, referred to as lipid bilayer stress (LBS). Through transcriptional and non-transcriptional mechanisms, the UPR upregulates the protein folding capacity of the ER and balances the production of proteins and lipids to maintain a functional secretory pathway. In this review, we discuss how UPR transducers sense unfolded proteins and LBS with a particular focus on their role as guardians of the secretory pathway.

show abstract

ERdj8 governs the size of autophagosomes during the formation process

Cited by 19 publications

References 55 publications

Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex

Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex

Autophagosome formation in relation to the endoplasmic reticulum

The Unfolded Protein Response as Guardian of the Secretory Pathway

Contact Info

Product

Resources

About