title: EphB receptors couple dendritic filopodia motility to synapse formation.
abstract: Motile dendritic filopodial processes are thought to be precursors of spine synapses, but how motility relates to cell-surface cues required for axon-dendrite recognition and synaptogenesis remains unclear. We demonstrate with dynamic imaging that loss of EphBs results in reduced motility of filopodia in cultured cortical neurons and brain slice. EphB knockdown and rescue experiments during different developmental time windows show that EphBs are required for synaptogenesis only when filopodia are most abundant and motile. In the context of EphB knockdown and reduced filopodia motility, independent rescue of either motility with PAK or of Eph-ephrin binding with an EphB2 kinase mutant is not sufficient to restore synapse formation. Strikingly, the combination of PAK and kinase-inactive EphB2 rescues synaptogenesis. Deletion of the ephrin-binding domain from EphB2 precludes rescue, indicating that both motility and trans-cellular interactions are required. Our findings provide a mechanistic link between dendritic filopodia motility and synapse differentiation.
authors.affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, 1114 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Kayser
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Nolt
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Dalva
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000502:physiology*; D004622:Embryo, Mammalian; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009154:Mutation; D009474:Neurons / Q000166:cytology; D011554:Pseudopodia / Q000502:physiology*; D051381:Rats; D036081:Receptors, Eph Family / Q000145:classification / Q000172:deficiency / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: D036081:Receptors, Eph Family