ER-phagy (Selective ER Autophagy) Project
Overview
ER-phagy is the selective autophagy of endoplasmic reticulum, mediated by specific receptor proteins that link ER membranes to the autophagy machinery. Most receptors were characterized 2017-2023, making this a relatively new field with recent discoveries.
Model Species
Primary: Homo sapiens (human)
- Most receptors characterized in human cells
- Disease relevance (neurodegeneration, viral infection)
Core Pathway Architecture
ER-phagy Receptors
Proteins that bridge ER to autophagosomes via LC3-interacting regions (LIRs):
- FAM134B (RETREG1) - Reticulon-like, sheet ER-phagy
- RTN3 - Reticulon 3, tubular ER
- SEC62 - Translocon-associated, recovER-phagy
- CCPG1 - Cell cycle progression gene 1
- TEX264 - Three-way junction ER-phagy
- ATL3 - Atlastin-3, tubular ER
Core Autophagy Machinery
- MAP1LC3B - LC3B, autophagosome marker
- GABARAP family - Alternative ATG8 family members
- ULK1 complex - Autophagy initiation
- ATG9A - Membrane source
ER Stress Connection
- ERN1 (IRE1α) - ER stress sensor
- EIF2AK3 (PERK) - ER stress kinase
Candidate Genes (~12-15)
| Gene | UniProt | Function |
|---|---|---|
| FAM134B | Q9H6L5 | ER-phagy receptor (sheets) |
| RTN3 | O95197 | ER-phagy receptor (tubules) |
| SEC62 | Q99442 | RecovER-phagy receptor |
| CCPG1 | Q9ULG6 | ER-phagy receptor |
| TEX264 | Q9Y6I9 | ER-phagy receptor |
| ATL3 | Q6DD88 | ER-phagy receptor |
| MAP1LC3B | Q9GZQ8 | Autophagosome protein |
| GABARAP | O95166 | ATG8 family |
| ULK1 | O75385 | Autophagy kinase |
| ATG9A | Q7Z3C6 | Membrane trafficking |
Key Recent Discoveries (2020+)
- TEX264 as ER-phagy receptor (2019-2020)
- ATL3 in tubular ER-phagy
- Structural basis of receptor-LC3 interactions
- ER-phagy in viral infection
Disease Relevance
- Hereditary sensory neuropathy (FAM134B mutations)
- ER storage diseases
- Viral infection (Zika, Dengue exploit ER-phagy)
Project Status
- [ ] Stub - needs gene folder setup