title: Receptor tyrosine kinase EphA7 is required for interneuron connectivity at specific subcellular compartments of granule cells.
abstract: 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.
authors.affiliation: Dept. Molecular Biology, Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstr. 55, 72770 Reutlingen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Beuter
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Mount Carmel, 31095, Israel.|The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Mount Carmel, 31095, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Ardi
authors.affiliation: The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Mount Carmel, 31095, Israel.
authors.forename: Omer
authors.initials: O
authors.lastname: Horovitz
authors.affiliation: Dept. Molecular Biology, Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstr. 55, 72770 Reutlingen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wuchter
authors.affiliation: Dept. Molecular Biology, Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstr. 55, 72770 Reutlingen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Keller
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Mount Carmel, 31095, Israel.
authors.forename: Rinki
authors.initials: R
authors.lastname: Saha
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Mount Carmel, 31095, Israel.
authors.forename: Kuldeep
authors.initials: K
authors.lastname: Tripathi
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Mount Carmel, 31095, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Anunu
authors.affiliation: The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Mount Carmel, 31095, Israel.
authors.forename: Orli
authors.initials: O
authors.lastname: Kehat
authors.affiliation: Dept. Molecular Biology, Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstr. 55, 72770 Reutlingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kriebel
authors.affiliation: Sagol Department of Neurobiology, University of Haifa, Mount Carmel, 31095, Israel.|The Institute for the Study of Affective Neuroscience (ISAN), University of Haifa, Mount Carmel, 31095, Israel.|Department of Psychology, University of Haifa, Mount Carmel, 31095, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Richter-Levin
authors.affiliation: Dept. Molecular Biology, Natural and Medical Sciences Institute at the University of Tübingen, Markwiesenstr. 55, 72770 Reutlingen, Germany.
authors.forename: Hansjürgen
authors.initials: H
authors.lastname: Volkmer
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D036141:Receptor, EphA7 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C073441:gephyrin; C546845:mTOR protein, rat; C093291:EPHA7 protein, rat; D036141:Receptor, EphA7; D058570:TOR Serine-Threonine Kinases