Open AccessReceptor tyrosine kinase EphA7 is required for interneuron connectivity at specific subcellular compartments of granule cells
Author(s) -
Simone Beuter,
Ziv Ardi,
Omer Horovitz,
Jennifer Wuchter,
Stefanie Keller,
Rinki Saha,
Kuldeep Tripathi,
Rachel Anunu,
Orli Kehat,
Martin Kriebel,
Gal RichterLevin,
Hansjürgen Volkmer
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep29710
Subject(s) - gephyrin , gabaergic , guanine nucleotide exchange factor , microbiology and biotechnology , neuroscience , interneuron , biology , inhibitory postsynaptic potential , postsynaptic potential , neurotransmission , glycine receptor , signal transduction , receptor , biochemistry , glycine , amino acid
Neuronal transmission is regulated by the local circuitry which is composed of principal neurons targeted at different subcellular compartments by a variety of interneurons. However, mechanisms that contribute to the subcellular localisation and maintenance of GABAergic interneuron terminals are poorly understood. Stabilization of GABAergic synapses depends on clustering of the postsynaptic scaffolding protein gephyrin and its interaction with the guanine nucleotide exchange factor collybistin. Lentiviral knockdown experiments in adult rats indicated that the receptor tyrosine kinase EphA7 is required for the stabilisation of basket cell terminals on proximal dendritic and somatic compartments of granular cells of the dentate gyrus. EphA7 deficiency and concomitant destabilisation of GABAergic synapses correlated with impaired long-term potentiation and reduced hippocampal learning. Reduced GABAergic innervation may be explained by an impact of EphA7 on gephyrin clustering. Overexpression or ephrin stimulation of EphA7 induced gephyrin clustering dependent on the mechanistic target of rapamycin (mTOR) which is an interaction partner of gephyrin. Gephyrin interactions with mTOR become released after mTOR activation while enhanced interaction with the guanine nucleotide exchange factor collybistin was observed in parallel. In conclusion, EphA7 regulates gephyrin clustering and the maintenance of inhibitory synaptic connectivity via mTOR signalling.