LAMP5 Fine-Tunes GABAergic Synaptic Transmission in Defined Circuits of the Mouse Brain.
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.
Aix-Marseille University, Centre National pour la Recherche Scientifique, IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille, France.
Marie-Catherine
MC
Tiveron
Aix-Marseille University, Centre National pour la Recherche Scientifique, IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille, France.
Corinne
C
Beurrier
Aix-Marseille University, Centre National pour la Recherche Scientifique, IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille, France.
Claire
C
Céni
Aix-Marseille University, Centre National pour la Recherche Scientifique, IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille, France.
Naly
N
Andriambao
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm U1104, CNRS UMR7280, 13288, Marseille, France.
Alexis
A
Combes
Neurogenesis and Physiopathology Group, INSERM U862, NeuroCentre Magendie, 33076, Bordeaux, France.
Muriel
M
Koehl
Aix-Marseille University, Centre National pour la Recherche Scientifique, IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille, France.
Nicolas
N
Maurice
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm U1104, CNRS UMR7280, 13288, Marseille, France.
Evelina
E
Gatti
Neurogenesis and Physiopathology Group, INSERM U862, NeuroCentre Magendie, 33076, Bordeaux, France.
Dhoher Nora
DN
Abrous
Aix-Marseille University, Centre National pour la Recherche Scientifique, IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille, France.
Lydia
L
Kerkerian-Le Goff
Centre d'Immunologie de Marseille-Luminy, Aix-Marseille Université UM2, Inserm U1104, CNRS UMR7280, 13288, Marseille, France.
Philippe
P
Pierre
Aix-Marseille University, Centre National pour la Recherche Scientifique, IBDM, Developmental Biology Institute of Marseille, UMR 7288, 13009, Marseille, France.
Harold
H
Cremer
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009830:Olfactory Bulb / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism; D009435:Synaptic Transmission; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism*
C000621376:LAMP5 protein, mouse; D051907:Lysosomal Membrane Proteins; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse