Single-Molecule Imaging Reveals Rapid Estradiol Action on the Surface Movement of AMPA Receptors in Live Neurons

Soma Godó; Klaudia Barabás; Ferenc Lengyel; Dávid Ernszt; Tamás Kovács; Miklós Kecskés; Csaba Varga; Tibor Z Jánosi; Géza Makkai; Gergely Kovács; Barbara Orsolits; Takahiro Fujiwara; Akihiro Kusumi; István M Ábrahám

doi:10.3389/fcell.2021.708715

Single-Molecule Imaging Reveals Rapid Estradiol Action on the Surface Movement of AMPA Receptors in Live Neurons

Front Cell Dev Biol. 2021 Sep 23:9:708715. doi: 10.3389/fcell.2021.708715. eCollection 2021.

Affiliations

¹ PTE-NAP Molecular Neuroendocrinology Research Group, Centre for Neuroscience, Szentágothai Research Center, Medical School, Institute of Physiology, University of Pécs, Pécs, Hungary.
² PTE-NAP Cortical Microcircuits Research Group, Institute of Physiology, Medical School, Centre for Neuroscience, Szentágothai Research Institute, Pécs, Hungary.
³ Laboratory of Neuroimmunology, Institute of Experimental Medicine of the Hungarian Academy of Sciences, Budapest, Hungary.
⁴ Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, Japan.
⁵ Membrane Cooperativity Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Onna, Japan.

Abstract

Gonadal steroid 17β-estradiol (E2) exerts rapid, non-genomic effects on neurons and strictly regulates learning and memory through altering glutamatergic neurotransmission and synaptic plasticity. However, its non-genomic effects on AMPARs are not well understood. Here, we analyzed the rapid effect of E2 on AMPARs using single-molecule tracking and super-resolution imaging techniques. We found that E2 rapidly decreased the surface movement of AMPAR via membrane G protein-coupled estrogen receptor 1 (GPER1) in neurites in a dose-dependent manner. The cortical actin network played a pivotal role in the GPER1 mediated effects of E2 on the surface mobility of AMPAR. E2 also decreased the surface movement of AMPAR both in synaptic and extrasynaptic regions on neurites and increased the synaptic dwell time of AMPARs. Our results provide evidence for understanding E2 action on neuronal plasticity and glutamatergic neurotransmission at the molecular level.

Keywords: 17β-estradiol; AMPAR; diffusion; single-molecule tracking; synapse.