Intrinsically Disordered Protein TEX264 Mediates ER-phagy

Area of Science:

• Cell Biology
• Molecular Biology
• Autophagy Research

Background:

• Selective autophagy degrades specific cellular components.
• LC3-interacting regions (LIRs) mediate substrate recognition by LC3 and GABARAP proteins on autophagosomes.
• Endoplasmic reticulum-phagy (ER-phagy) targets the ER for autophagic degradation.

Purpose of the Study:

• To identify novel receptors involved in selective autophagy, specifically ER-phagy.
• To characterize the function and mechanism of identified ER-phagy receptors.

Main Methods:

• Differential interactome screening using wild-type LC3B and a LIR-deficient mutant.
• Identification and characterization of TEX264 as an ER-phagy receptor.
• Genetic deletion studies (TEX264, FAM134B, CCPG1) to assess ER-phagy blockage.
• Analysis of TEX264's structural requirements for ER-phagy function.

Main Results:

• TEX264 was identified as a novel receptor for ER-phagy.
• TEX264, an ER protein with a transmembrane domain and LIR motif, efficiently binds LC3/GABARAP proteins.
• TEX264 exhibits broader expression than previously known ER-phagy receptors.
• Deletion of TEX264 significantly impairs ER-phagy; combined deletion with FAM134B and CCPG1 almost completely blocks it.
• An intrinsically disordered region of TEX264 is crucial for bridging ER and autophagosomal membranes.

Conclusions:

• TEX264 is a major and essential receptor for ER-phagy.
• The findings elucidate a key mechanism in selective ER degradation.
• TEX264's unique structural features contribute to its vital role in ER homeostasis via autophagy.