A role for Mints in transmitter release: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission
AUTOR(ES)
Ho, Angela
FONTE
The National Academy of Sciences
RESUMO
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 γ-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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=298786Documentos Relacionados
- Histamine H1 receptor knockout mice exhibit impaired spatial memory in the eight-arm radial maze
- Mice deficient for prion protein exhibit normal neuronal excitability and synaptic transmission in the hippocampus.
- Asynchronous transmitter release: control of exocytosis and endocytosis at the salamander rod synapse.
- Impaired Conditioned Taste Aversion Learning in Spinophilin Knockout Mice
- Septin 11 Is Present in GABAergic Synapses and Plays a Functional Role in the Cytoarchitecture of Neurons and GABAergic Synaptic Connectivity*