A role for Mints in transmitter release: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission

Angela Ho, Wade Morishita, Robert E Hammer, Robert C. Malenka, Thomas C. Südhof

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Mints (also called X11-like proteins) are adaptor proteins composed of divergent N-terminal sequences that bind to synaptic proteins such as CASK (Mint 1 only) and Munc18-1 (Mints 1 and 2) and conserved C-terminal PTB- and PDZ-domains that bind to widely distributed proteins such as APP, presenilins, and Ca2+ channels (all Mints). We find that Mints 1 and 2 are similarly expressed in most neurons except for inhibitory interneurons that contain selectively high levels of Mint 1. Using knockout mice, we show that deletion of Mint 1 does not impair survival or alter the overall brain architecture, arguing against an essential developmental function of the Mint 1-CASK complex. In electrophysiological recordings in the hippocampus, we observed no changes in short- or long-term synaptic plasticity in excitatory synapses from Mint 1-deficient mice and detected no alterations in the ratio of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to N-methyl-D-aspartate (NMDA) receptor-mediated synaptic currents. Thus the Mint 1-CASK complex is not required for AMPA- and NMDA-receptor functions or for synaptic plasticity in excitatory synapses. In inhibitory synapses, however, we uncovered an ≈3-fold increase in presynaptic paired-pulse depression, suggesting that deletion of Mint 1 impairs the regulation of 7-aminobutyric acid release. Our data indicate that Mints 1 and 2 perform redundant synaptic functions that become apparent in Mint 1-deficient mice in inhibitory interneurons because these neurons selectively express higher levels of Mint 1 than Mint 2.

Original languageEnglish (US)
Pages (from-to)1409-1414
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number3
DOIs
StatePublished - Feb 4 2003

ASJC Scopus subject areas

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