Long-term potentiation reconstituted with an artificial TARP/PSD-95 complex

Anagh Sinha Ravi; Menglong Zeng; Xudong Chen; Gerardo Sandoval; Javier Diaz-Alonso; Mingjie Zhang; Roger A Nicoll

doi:10.1016/j.celrep.2022.111483

Long-term potentiation reconstituted with an artificial TARP/PSD-95 complex

Cell Rep. 2022 Oct 11;41(2):111483. doi: 10.1016/j.celrep.2022.111483.

Authors

Anagh Sinha Ravi¹, Menglong Zeng², Xudong Chen², Gerardo Sandoval³, Javier Diaz-Alonso⁴, Mingjie Zhang⁵, Roger A Nicoll⁶

Affiliations

¹ Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA, USA.
² Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
³ Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine, CA, USA.
⁴ Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA, USA; Center for the Neurobiology of Learning and Memory, University of California at Irvine, Irvine, CA, USA. Electronic address: [email protected].
⁵ Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen 518036, China; School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
⁶ Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, CA, USA. Electronic address: [email protected].

Abstract

The critical role of AMPA receptor (AMPAR) trafficking in long-term potentiation (LTP) of excitatory synaptic transmission is now well established, but the underlying molecular mechanism is still uncertain. Recent research suggests that PSD-95 captures AMPARs via an interaction with the AMPAR auxiliary subunits-transmembrane AMPAR regulatory proteins (TARPs). To determine if such interaction is a core minimal component of the AMPAR trafficking and LTP mechanism, we engineered artificial binding partners, which individually were biochemically and functionally dead but which, when expressed together, rescue binding and both basal synaptic transmission and LTP. These findings establish the TARP/PSD-95 complex as an essential interaction underlying AMPAR trafficking and LTP.

Keywords: AMPA receptor trafficking; AMPAR; CP: Neuroscience; GluA1; LTP; MAGUK; PSD-95; TARP; postsynaptic density; synaptic transmission.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Disks Large Homolog 4 Protein / metabolism
Long-Term Potentiation* / physiology
Nuclear Proteins / metabolism
Receptors, AMPA* / metabolism
Synapses / metabolism
Synaptic Transmission / physiology

Substances

Disks Large Homolog 4 Protein
Nuclear Proteins
Receptors, AMPA
TARP

Abstract

Publication types

MeSH terms

Substances

Grants and funding