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The Kappa Opioid Receptor pp 83–96Cite as

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

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 271))

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.

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Abbreviations

AAA:

ATPases associated with diverse cellular activities

Atg8:

The yeast autophagy protein 8

CHO-FLAG-KOR:

CHO cell line stably expressing FLAG-hKOR

DOR:

Delta opioid receptor

ER:

Endoplasmic reticulum

GABARAP:

GABAA receptor-associated protein

GABARAPL1:

GABAA receptor-associated protein like 1

GATE16:

Golgi-associated ATPase enhancer of 16 kDa

GEC1:

Glandular epithelial cell 1

GOS-28:

Golgi-specific v-SNARE of 28 kDa

GST:

Glutathione S-transferase

hKOR:

Human KOR

KCT:

KOR C-tail

KOR:

Kappa opioid receptor

LC3:

Light chain 3 of MAP 1A/1B

MAPs:

Microtubule-associated proteins

MOR:

Mu opioid receptor

NSF:

N-ethylmaleimide-sensitive factor

SNARE:

Soluble N-ethylmaleimide sensitive factor attachment protein receptor

α-SNAP:

Soluble NSF attachment protein

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Acknowledgements

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

Declarations of Interest: None.

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Authors and Affiliations

  1. Center for Substance Abuse Research and Department of Pharmacology, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA

    Peng Huang, Chongguang Chen & Lee-Yuan Liu-Chen

  2. Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA

    Chunxia Zhao & Sidney W. Whiteheart

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  1. Peng Huang
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  2. Chunxia Zhao
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  3. Chongguang Chen
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  4. Sidney W. Whiteheart
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  5. Lee-Yuan Liu-Chen
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Correspondence to Lee-Yuan Liu-Chen .

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Editors and Affiliations

  1. Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Lee-Yuan Liu-Chen

  2. Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA

    Saadet Inan

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Huang, P., Zhao, C., Chen, C., Whiteheart, S.W., Liu-Chen, LY. (2020). Does GEC1 Enhance Expression and Forward Trafficking of the Kappa Opioid Receptor (KOR) via Its Ability to Interact with NSF Directly?. In: Liu-Chen, LY., Inan, S. (eds) The Kappa Opioid Receptor. Handbook of Experimental Pharmacology, vol 271. Springer, Cham. https://doi.org/10.1007/164_2020_398

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