Does GEC1 Enhance Expression and Forward Trafficking of the Kappa Opioid Receptor (KOR) via Its Ability to Interact with NSF Directly?

Peng Huang, Chunxia Zhao, Chongguang Chen, Sidney W. Whiteheart, Lee Yuan Liu-Chen

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

We reported previously that GEC1 (glandular epithelial cell 1), a member of microtubule-associated proteins (MAPs), interacted directly with the C-tail of KOR (KCT) and tubulin and enhanced cell surface expression of KOR in CHO cells by facilitating its trafficking along the export pathway. Two GEC1 analogs (GABARAP and GATE16) were also shown to increase KOR expression. In addition, to understand the underlying mechanism, we demonstrated that N-ethylmaleimide-sensitive factor (NSF), an essential component for membrane fusion, co-immunoprecipitated with GEC1 from brain extracts. In this study, using pull-down techniques, we have found that (1) GEC1 interacts with NSF directly and prefers the ADP-bound NSF to the ATP-bound NSF; (2) D1 and/or D2 domain(s) of NSF interact with GEC1, but the N domain of NSF does not; (3) NSF does not interact with KCT directly, but forms a protein complex with KCT via GEC1; (4) NSF and/or α-SNAP do not affect KCT-GEC1 interaction. Thus, GEC1 (vs the α-SNAP/SNAREs complex) binds to NSF in distinctive ways in terms of the ADP- or ATP-bound form and domains of NSF involved. In conclusion, GEC1 may, via its direct interactions with KOR, NSF, and tubulin, enhance trafficking and fusion of KOR-containing vesicles selectively along the export pathway, which leads to increase in surface expression of KOR. GABARAP and GATE16 may enhance KOR expression in a similar way.

Original languageEnglish
Title of host publicationHandbook of Experimental Pharmacology
Pages83-96
Number of pages14
DOIs
StatePublished - 2022

Publication series

NameHandbook of Experimental Pharmacology
Volume271
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Bibliographical note

Funding Information:
Acknowledgements Supported by NIH grants R01 DA17302, R01 DA041359 and P30 DA13429 (LYLC), R01 NS046242 (SWW).

Publisher Copyright:
© 2020, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Keywords

  • GABARAP
  • GATE16
  • GEC1
  • Kappa opioid receptor
  • NSF
  • Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics (all)

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