title: A dual shaping mechanism for postsynaptic ephrin-B3 as a receptor that sculpts dendrites and synapses.
abstract: As the neural network becomes wired, postsynaptic signaling molecules are thought to control the growth of dendrites and synapses. However, how these molecules are coordinated to sculpt postsynaptic structures is less well understood. We find that ephrin-B3, a transmembrane ligand for Eph receptors, functions postsynaptically as a receptor to transduce reverse signals into developing dendrites of mouse hippocampal neurons. Both tyrosine phosphorylation-dependent GRB4 SH2/SH3 adaptor-mediated signals and PSD-95-discs large-zona occludens-1 (PDZ) domain-dependent signals are required for inhibition of dendrite branching, whereas only PDZ interactions are necessary for spine formation and excitatory synaptic function. PICK1 and syntenin, two PDZ domain proteins, participate with ephrin-B3 in these postsynaptic activities. PICK1 has a specific role in spine and synapse formation, and syntenin promotes both dendrite pruning and synapse formation to build postsynaptic structures that are essential for neural circuits. The study thus dissects ephrin-B reverse signaling into three distinct intracellular pathways and protein-protein interactions that mediate the maturation of postsynaptic neurons.
authors.affiliation: Department of Developmental Biology, Kent Waldrep Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Nan-Jie
authors.initials: NJ
authors.lastname: Xu
authors.forename: Suya
authors.initials: S
authors.lastname: Sun
authors.forename: Jay R
authors.initials: JR
authors.lastname: Gibson
authors.forename: Mark
authors.initials: M
authors.lastname: Henkemeyer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D003712:Dendrites / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D049229:Dendritic Spines / Q000648:ultrastructure; D036388:Ephrin-B2 / Q000235:genetics; D036389:Ephrin-B3 / Q000235:genetics / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D054731:PDZ Domains / Q000235:genetics / Q000502:physiology; D037121:Plant Lectins / Q000235:genetics / Q000378:metabolism; D016622:Silver Staining / Q000379:methods; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D053676:Syntenins / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D018909:src Homology Domains / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D036388:Ephrin-B2; D036389:Ephrin-B3; D009687:Nuclear Proteins; D037121:Plant Lectins; C091822:Prkcabp protein, mouse; D053676:Syntenins; C034981:tomato lectin