Hva22, a REEP family protein in fission yeast, promotes reticulophagy in collaboration with a receptor protein

ABSTRACT

The endoplasmic reticulum (ER) undergoes selective autophagy called reticulophagy or ER-phagy. Multiple reticulon- and receptor expression enhancing protein (REEP)-like ER-shaping proteins, including budding yeast Atg40, serve as reticulophagy receptors that stabilize the phagophore on the ER by interacting with phagophore-conjugated Atg8. Additionally, they facilitate phagophore engulfment of the ER by remodeling ER morphology. We reveal that Hva22, a REEP family protein in fission yeast, promotes reticulophagy without Atg8-binding capacity. The role of Hva22 in reticulophagy can be replaced by expressing Atg40 independently of its Atg8-binding ability. Conversely, adding an Atg8-binding sequence to Hva22 enables it to substitute for Atg40 in budding yeast. Thus, the phagophore-stabilizing and ER-shaping activities, both of which Atg40 solely contains, are divided between two separate factors, receptors and Hva22, respectively, in fission yeast.

Abbreviations: AIM: Atg8-family interacting motif; Atg: autophagy related; DTT: dithiothreitol; ER: endoplasmic reticulum GFP: green fluorescent protein; NAA: 1-naphthaleneacetic acid; REEP: receptor expression enhancing protein; RFP: red fluorescent protein; UPR: unfolded protein response.

KEYWORDS:

• Atg40
• autophagy
• endoplasmic reticulum (ER)
• ER-phagy
• ER-shaping
• Hva22
• REEP
• reticulon
• reticulophagy
• yeasts

Acknowledgements

We thank Kazuhiro Shiozaki, Hitoshi Nakatogawa, and the National Bio-Resource Project (NBRP, Japan) for providing materials. We also thank Nobuo Noda for useful advice.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The work was supported by the Japan Society for the Promotion of Science [20K06552]; Japan Society for the Promotion of Science [19H05712]; Japan Society for the Promotion of Science [22H02615]; Takeda Science Foundation