Annexin A2 traps mu-opioid receptors in recycling endosomes upon remifentanil-induced internalization

Idy H T Ho1,2, Lhotse H L Ng1,2, Xiaojie Cheng1

  • 1Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong Special Administrative Region, China.

Insights

Annexin A2 (ANXA2) is a newly identified protein that interacts with the Mu-opioid receptor 1 (MOR1). ANXA2 regulates MOR1

Area of Science:

  • Cellular Biology
  • Molecular Pharmacology
  • Neuroscience

Background:

  • The Mu-opioid receptor 1 (MOR1) is a key target for opioid analgesics.
  • Understanding MOR1 regulation is crucial for developing safer pain management strategies.
  • Sub-cellular localization of MOR1 influences its signaling and downstream effects.

Purpose of the Study:

  • To identify novel proteins interacting with MOR1.
  • To investigate the role of ANXA2 in regulating MOR1 sub-cellular localization.
  • To determine the effect of remifentanil exposure on the ANXA2-MOR1 interaction.

Main Methods:

  • Co-immunoprecipitation assays to identify MOR1-interacting proteins.
  • Confocal microscopy to visualize sub-cellular localization of MOR1 and ANXA2.
  • Pharmacological treatments with remifentanil.

Main Results:

  • Annexin A2 (ANXA2) was identified as a novel MOR1-interacting protein.
  • ANXA2 retains MOR1 in late recycling endosomes following remifentanil exposure.
  • This interaction impacts MOR1 trafficking and availability at the cell surface.

Conclusions:

  • ANXA2 is a critical regulator of MOR1 sub-cellular localization.
  • The ANXA2-MOR1 interaction provides a new target for modulating opioid receptor function.
  • Understanding this mechanism may lead to improved opioid-based therapeutics.

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