Intrinsically Disordered Protein TEX264 Mediates ER-phagy

Chino, Haruo; Hatta, Tomohisa; Natsume, Tohru; Mizushima, Noboru

doi:10.1016/j.molcel.2019.03.033

Cited by 260 publications

(352 citation statements)

References 69 publications

Supporting

Mentioning

341

Contrasting

Order By: Relevance

“…On the contrary, CCPG1, SEC62 and TEX264 are transmembrane (TM) proteins with a cytosolic, ER membrane and ER luminal domains with no reported function in shaping ER membranes. Notably, TEX264 appears to be enriched at three‐way junctions . SEC62 is a constituent of the translocon complex‐regulating protein import in the mammalian ER.…”

Section: The ‘Er‐phagy’ Pathwaymentioning

confidence: 99%

Emerging lysosomal pathways for quality control at the endoplasmic reticulum

2019

View full text Add to dashboard Cite

Protein misfolding occurring in the endoplasmic reticulum (ER) might eventually lead to aggregation and cellular distress, and is a primary pathogenic mechanism in multiple human disorders. Mammals have developed evolutionary‐conserved quality control mechanisms at the level of the ER. The best characterized is the ER‐associated degradation (ERAD) pathway, through which misfolded proteins translocate from the ER to the cytosol and are subsequently proteasomally degraded. However, increasing evidence indicates that additional quality control mechanisms apply for misfolded ER clients that are not eligible for ERAD. This review focuses on the alternative, ERAD‐independent, mechanisms of clearance of misfolded polypeptides from the ER. These processes, collectively referred to as ER‐to‐lysosome–associated degradation, involve ER‐phagy, microautophagy or vesicular transport. The identification of the underlying molecular mechanisms is particularly important for developing new therapeutic approaches for human diseases associated with protein aggregate formation.

show abstract

Section: The ‘Er‐phagy’ Pathwaymentioning

confidence: 99%

Emerging lysosomal pathways for quality control at the endoplasmic reticulum

2019

View full text Add to dashboard Cite

show abstract

“…Despite the differences between the various ERphagy receptors, there is one common feature: they contain an intrinsic disordered region, which generally has multiple functions including protein-protein interactions and membranes curving [39]. So far, the intrinsic disordered region seems to be a common feature to almost all ER-phagy receptors (this remains to be confirmed for ATL3) and this characteristic may be responsible for the ability of these proteins to attract autophagic membranes [27]. As more ER-phagy receptors are uncovered, likely with different ER sublocalizations, modes of action and substrates specificity, this hypothesis will be put to the test.…”

Section: The History Of Er-phagymentioning

confidence: 99%

“…Only in recent years, after the characterization of the first ER-phagy receptors (see next paragraph), FAM134B in mammals and ATG39 and ATG40 in yeast [25,26], the molecular basis of ER-phagy was revealed and its full biological importance began to be recognized [10]. Several mammalian ER-phagy receptors have been identified so far: SEC62, RTN3 (its long isoform RTN3L), CCPG1, ATL3, and TEX264 [27][28][29][30][31][32] (Fig. 1A,B).…”

Section: The History Of Er-phagymentioning

confidence: 99%

“…On the other hand, TM receptors span the entirety of the ER membrane with a portion of the protein facing the intraluminal space. IM proteins include: ATL3, FAM134B, RTN3L; and TM proteins include: CCPG1, SEC62, TEX264, respectively [3, 25,27,29,30,34,35]. Members of the IM group have well known functions in shaping ER subdomains, modulating tubule/sheet ratios as well as tubule branching [3,35].…”

Section: The History Of Er-phagymentioning

confidence: 99%

See 1 more Smart Citation

The various shades of ER‐phagy

Stolz

2019

The FEBS Journal

View full text Add to dashboard Cite

Endoplasmic reticulum (ER) is a large and dynamic cellular organelle. ER morphology consists of sheets, tubules, matrixes, and contact sites shared with other membranous organelles. The capacity of the ER to fulfill its numerous biological functions depends on its continuous remodeling and the quality control of its proteome. Selective turnover of the ER by autophagy, termed ER‐phagy, plays an important role in maintaining ER homeostasis. ER network integrity and turnover rely on specific ER‐phagy receptors, which influence and coordinate alterations in ER morphology and the degradation of ER contents and membranes via the lysosome, by interacting with the LC3/GABARAP family. In this commentary, we discuss general principles and identify the major players in this recently characterized form of selective autophagy, while simultaneously highlighting open questions in the field.

show abstract

“…While the topological equivalence of microautophagy and other ESCRT-dependent processes is compelling, a direct involvement of ESCRT machinery in microautophagy has been difficult to demonstrate. ER-phagy, the selective autophagy of ER, can occur by macroautophagy in both yeast and mammals, and several macro-ER-phagy receptors have been identified (Hamasaki et al, 2005;Khaminets et al, 2015;Mochida et al, 2015;Fumagalli et al, 2016;Grumati et al, 2017;Smith et al, 2018;Chino et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

ESCRT machinery mediates selective microautophagy of endoplasmic reticulum

Schäfer

Schessner

Bircham

et al. 2019

Preprint

View full text Add to dashboard Cite

ER‐phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER‐phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro‐ER‐phagy has been discovered, the molecules and mechanisms mediating micro‐ER‐phagy remain unknown. Here, we first show that micro‐ER‐phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1‐Spo7 phosphatase complex and the ESCRT machinery as key components for micro‐ER‐phagy. Third, we demonstrate that macro‐ and micro‐ER‐phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro‐ER‐phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis.

show abstract

Intrinsically Disordered Protein TEX264 Mediates ER-phagy

Cited by 260 publications

References 69 publications

Emerging lysosomal pathways for quality control at the endoplasmic reticulum

Emerging lysosomal pathways for quality control at the endoplasmic reticulum

The various shades of ER‐phagy

ESCRT machinery mediates selective microautophagy of endoplasmic reticulum

Contact Info

Product

Resources

About