title: Transsynaptic coordination of synaptic growth, function, and stability by the L1-type CAM Neuroglian.
abstract: The precise control of synaptic connectivity is essential for the development and function of neuronal circuits. While there have been significant advances in our understanding how cell adhesion molecules mediate axon guidance and synapse formation, the mechanisms controlling synapse maintenance or plasticity in vivo remain largely uncharacterized. In an unbiased RNAi screen we identified the Drosophila L1-type CAM Neuroglian (Nrg) as a central coordinator of synapse growth, function, and stability. We demonstrate that the extracellular Ig-domains and the intracellular Ankyrin-interaction motif are essential for synapse development and stability. Nrg binds to Ankyrin2 in vivo and mutations reducing the binding affinities to Ankyrin2 cause an increase in Nrg mobility in motoneurons. We then demonstrate that the Nrg-Ank2 interaction controls the balance of synapse growth and stability at the neuromuscular junction. In contrast, at a central synapse, transsynaptic interactions of pre- and postsynaptic Nrg require a dynamic, temporal and spatial, regulation of the intracellular Ankyrin-binding motif to coordinate pre- and postsynaptic development. Our study at two complementary model synapses identifies the regulation of the interaction between the L1-type CAM and Ankyrin as an important novel module enabling local control of synaptic connectivity and function while maintaining general neuronal circuit architecture.
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Enneking
authors.forename: Sirisha R
authors.initials: SR
authors.lastname: Kudumala
authors.forename: Eliza
authors.initials: E
authors.lastname: Moreno
authors.forename: Raiko
authors.initials: R
authors.lastname: Stephan
authors.forename: Jana
authors.initials: J
authors.lastname: Boerner
authors.forename: Tanja A
authors.initials: TA
authors.lastname: Godenschwege
authors.forename: Jan
authors.initials: J
authors.lastname: Pielage
mesh_terms: D000200:Action Potentials; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000502:physiology*; D049108:Cell Enlargement; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology*; D008969:Molecular Sequence Data; D009469:Neuromuscular Junction / Q000502:physiology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission
chemical_list: C498993:Ank2 protein, Drosophila; D017487:Ankyrins; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; C061745:Nrg protein, Drosophila