LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain.
PLoS ONE. 2016-06-07; 11(6): e0157052
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1. PLoS One. 2016 Jun 7;11(6):e0157052. doi: 10.1371/journal.pone.0157052.
LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse
Tiveron MC(1), Beurrier C(1), Céni C(1), Andriambao N(1), Combes A(2), Koehl
M(3), Maurice N(1), Gatti E(2), Abrous DN(3), Kerkerian-Le Goff L(1), Pierre
P(2), Cremer H(1).
(1)Aix-Marseille University, Centre National pour la Recherche Scientifique,
IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille,
(2)Centre d’Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm
U1104, CNRS UMR7280, 13288, Marseille, France.
(3)Neurogenesis and Physiopathology Group, INSERM U862, NeuroCentre Magendie,
33076, Bordeaux, France.
LAMP5 is member of the LAMP family of membrane proteins. In contrast to the
canonical members of this protein family, LAMP1 and LAMP2, which show widespread
expression in many tissues, LAMP 5 is brain specific in mice. In C. elegans, the
LAMP5 ortholog UNC-46 has been suggested to act a trafficking chaperone,
essential for the correct targeting of the nematode vesicular GABA-transporter
UNC-47. We show here that in the mouse brain LAMP5 is expressed in subpopulations
of GABAergic forebrain neurons in the striato-nigral system and the olfactory
bulb. The protein was present at synaptic terminals, overlapping with the
mammalian vesicular GABA-transporter VGAT. In LAMP5-deficient mice localization
of the transporter was unaffected arguing against a conserved role in VGAT
trafficking. Electrophysiological analyses in mutants showed alterations in short
term synaptic plasticity suggesting that LAMP5 is involved in controlling the
dynamics of evoked GABAergic transmission. At the behavioral level, LAMP5 mutant
mice showed decreased anxiety and deficits in olfactory discrimination.
Altogether, this work implicates LAMP5 function in GABAergic neurotransmission in
defined neuronal subpopulations.
PMID: 27272053 [Indexed for MEDLINE]