Connecting reticulophagy and neuronal NTRK2/TrkB signaling

ABSTRACT

Tightly regulated cell surface expression of NTRK2/TrkB provides a mechanism for fine-tuning cellular responses to the neurotrophic factor BDNF. Recently, the degradation of NTRK2 by reticulophagy has been identified as a mechanism to limit its availability for trafficking to the cell membrane. The ER-chaperone CANX (calnexin) delivers NTRK2 to the reticulophagy receptor RETREG1/Fam134b for lysosomal degradation. Upon phosphorylation of CANX, NTRK2 is released from this complex, which facilitates its cell surface transport. These results identify a novel role for CANX in regulating the cell surface expression of NTRK2 and imply a function for reticulophagy that goes beyond regulating the degradation of misfolded proteins within the ER.

KEYWORDS:

• Calnexin
• Fam134b
• NTRK2/TrkB signaling
• BDNF
• ER-phagy
• EGF

Acknowledgements

The graphical abstract was created with BioRender.com.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

P.L. was supported by Deutsche Forschungsgemeinschaft (DFG) grant DFG LU 2347/3-1. M.S. received support from the DFG through project 424778381 (SFB-TRR 295, A05) and projects SE 697/5-2 and SE 697/7-1.