TARP modulation of synaptic AMPA receptor trafficking and gating depends on multiple intracellular domains.

Abstract:

:Previous work has established stargazin and its related family of transmembrane AMPA receptor regulatory proteins (TARPs) as auxiliary subunits of AMPA receptors (AMPARs) that control synaptic strength both by targeting AMPARs to synapses through an intracellular PDZ-binding motif and by modulating their gating through an extracellular domain. However, TARPs gamma-2 and gamma-8 differentially regulate the synaptic targeting of AMPARs, despite having identical PDZ-binding motifs. Here, we investigate the structural elements that contribute to this functional difference between TARP subtypes by using domain transplantation and truncation. We identify a component of synaptic AMPAR trafficking that is independent of the TARP C-terminal PDZ-binding motif, and we establish previously uncharacterized roles for the TARP intracellular N terminus, loop, and C terminus in modulating both the trafficking and gating of synaptic AMPARs.

authors

Milstein AD,Nicoll RA

doi

10.1073/pnas.0905570106

subject

Has Abstract

pub_date

2009-07-07 00:00:00

pages

11348-51

issue

27

eissn

0027-8424

issn

1091-6490

pii

0905570106

journal_volume

106

pub_type

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