Control of Synaptic Connectivity by a Network of Drosophila IgSF Cell Surface Proteins

We have defined a network of interacting Drosophila cell surface proteins in which a 21-member IgSF subfamily, the Dprs, binds to a nine-member subfamily, the DIPs. The structural basis of the Dpr-DIP interaction code appears to be dictated by shape complementarity within the Dpr-DIP binding interface. Each of the six dpr and DIP genes examined here is expressed by a unique subset of larval and pupal neurons. In the neuromuscular system, interactions between Dpr11 and DIP-γ affect presynaptic terminal development, trophic factor responses, and neurotransmission. In the visual system, dpr11 is selectively expressed by R7 photoreceptors that use Rh4 opsin (yR7s). Their primary synaptic targets, Dm8 amacrine neurons, express DIP-γ. In dpr11 or DIP-γ mutants, yR7 terminals extend beyond their normal termination zones in layer M6 of the medulla. DIP-γ is also required for Dm8 survival or differentiation. Our findings suggest that Dpr-DIP interactions are important determinants of synaptic connectivity.

[1]  Z. Otwinowski,et al.  Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[2]  J. Abrahams,et al.  Methods used in the structure determination of bovine mitochondrial F1 ATPase. , 1996, Acta crystallographica. Section D, Biological crystallography.

[3]  M. Arbeitman,et al.  Genomic and Functional Studies of Drosophila Sex Hierarchy Regulated Gene Expression in Adult Head and Nervous System Tissues , 2007, PLoS genetics.

[4]  Masahito Yamagata,et al.  SIDEKICK 2 DIRECTS FORMATION OF A RETINAL CIRCUIT THAT DETECTS DIFFERENTIAL MOTION , 2015, Nature.

[5]  Shin-ya Takemura,et al.  Ig Superfamily Ligand and Receptor Pairs Expressed in Synaptic Partners in Drosophila , 2015, Cell.

[6]  T. Tabata,et al.  Daughters against dpp modulates dpp organizing activity in Drosophila wing development , 1997, Nature.

[7]  Mala Murthy,et al.  The Translational Repressors Nanos and Pumilio Have Divergent Effects on Presynaptic Terminal Growth and Postsynaptic Glutamate Receptor Subunit Composition , 2009, The Journal of Neuroscience.

[8]  J. Palka,et al.  Defective Proboscis Extension Response (DPR), a Member of the Ig Superfamily Required for the Gustatory Response to Salt , 2002, The Journal of Neuroscience.

[9]  H. Wolfson,et al.  Shape complementarity at protein–protein interfaces , 1994, Biopolymers.

[10]  P. Zwart,et al.  Towards automated crystallographic structure refinement with phenix.refine , 2012, Acta crystallographica. Section D, Biological crystallography.

[11]  George M Sheldrick,et al.  Substructure solution with SHELXD. , 2002, Acta crystallographica. Section D, Biological crystallography.

[12]  K. Fischbach,et al.  The optic lobe of Drosophila melanogaster. I. A Golgi analysis of wild-type structure , 1989, Cell and Tissue Research.

[13]  B. Ganetzky,et al.  Nervous Wreck Interacts with Thickveins and the Endocytic Machinery to Attenuate Retrograde BMP Signaling during Synaptic Growth , 2008, Neuron.

[14]  Kai Zinn,et al.  Development and plasticity of the Drosophila larval neuromuscular junction , 2013, Wiley interdisciplinary reviews. Developmental biology.

[15]  G. Tavosanis,et al.  Assessing the Role of Cell-Surface Molecules in Central Synaptogenesis in the Drosophila Visual System , 2013, PloS one.

[16]  P. Emsley,et al.  Features and development of Coot , 2010, Acta crystallographica. Section D, Biological crystallography.

[17]  C. Goodman,et al.  Slit Is the Midline Repellent for the Robo Receptor in Drosophila , 1999, Cell.

[18]  Seungbok Lee,et al.  Spartin Regulates Synaptic Growth and Neuronal Survival by Inhibiting BMP-Mediated Microtubule Stabilization , 2013, Neuron.

[19]  D. Owald,et al.  Maturation of active zone assembly by Drosophila Bruchpilot , 2009, The Journal of cell biology.

[20]  I. Wilson,et al.  The Molecular Interaction of CAR and JAML Recruits the Central Cell Signal Transducer PI3K , 2010, Science.

[21]  Robert A. Carrillo,et al.  Presynaptic Activity and CaMKII Modulate Retrograde Semaphorin Signaling and Synaptic Refinement , 2010, Neuron.

[22]  Eric Blanc,et al.  Automated structure solution with autoSHARP. , 2007, Methods in molecular biology.

[23]  Karin M Reinisch,et al.  Insights into MHC class I peptide loading from the structure of the tapasin-ERp57 thiol oxidoreductase heterodimer. , 2009, Immunity.

[24]  C. Goodman,et al.  Plexin A Is a Neuronal Semaphorin Receptor that Controls Axon Guidance , 1998, Cell.

[25]  K. Garcia,et al.  An Extracellular Interactome of Immunoglobulin and LRR Proteins Reveals Receptor-Ligand Networks , 2013, Cell.

[26]  S. Zipursky,et al.  Sequential Axon-Derived Signals Couple Target Survival and Layer Specificity in the Drosophila Visual System , 2014, Neuron.

[27]  P. Gregersen,et al.  Structural biology of shared cytokine receptors. , 2009, Annual review of immunology.

[28]  J. Taipale,et al.  A versatile platform for creating a comprehensive UAS-ORFeome library in Drosophila , 2013, Development.

[29]  Louis K. Scheffer,et al.  A visual motion detection circuit suggested by Drosophila connectomics , 2013, Nature.

[30]  Liqun Luo,et al.  Structure of the vertical and horizontal system neurons of the lobula plate in Drosophila , 2002, The Journal of comparative neurology.

[31]  B. Ganetzky,et al.  Satellite signaling at synapses , 2008, Fly.

[32]  Benjamin W Booth,et al.  A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila , 2015, eLife.

[33]  Esteban O. Mazzoni,et al.  Stochastic spineless expression creates the retinal mosaic for colour vision , 2006, Nature.

[34]  K. Garcia,et al.  Extracellular Architecture of the SYG-1/SYG-2 Adhesion Complex Instructs Synaptogenesis , 2014, Cell.

[35]  David Jukam,et al.  Dissection and immunohistochemistry of larval, pupal and adult Drosophila retinas. , 2012, Journal of visualized experiments : JoVE.

[36]  S. Almo,et al.  Structure of Nectin-2 reveals determinants of homophilic and heterophilic interactions that control cell–cell adhesion , 2012, Proceedings of the National Academy of Sciences.

[37]  G. Davis,et al.  Unrestricted Synaptic Growth in spinster—a Late Endosomal Protein Implicated in TGF-β-Mediated Synaptic Growth Regulation , 2002, Neuron.

[38]  Andreas S. Thum,et al.  The Neural Substrate of Spectral Preference in Drosophila , 2008, Neuron.

[39]  L. Luo,et al.  piggyBac-based mosaic screen identifies a postmitotic function for cohesin in regulating developmental axon pruning. , 2008, Developmental cell.

[40]  Claude Desplan,et al.  The Color-Vision Circuit in the Medulla of Drosophila , 2008, Current Biology.

[41]  G. Rubin,et al.  A directional tuning map of Drosophila elementary motion detectors , 2013, Nature.

[42]  The translational regulator Cup controls NMJ presynaptic terminal morphology , 2015, Molecular and Cellular Neuroscience.

[43]  E. Suzuki,et al.  A Screen of Cell-Surface Molecules Identifies Leucine-Rich Repeat Proteins as Key Mediators of Synaptic Target Selection , 2008, Neuron.

[44]  Nele A. Haelterman,et al.  MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes , 2011, Nature Methods.

[45]  Xiaozhong Peng,et al.  Crystal Structure of the V Domain of Human Nectin-like Molecule-1/Syncam3/Tsll1/Igsf4b, a Neural Tissue-specific Immunoglobulin-like Cell-Cell Adhesion Molecule* , 2006, Journal of Biological Chemistry.

[46]  Ian A. Meinertzhagen,et al.  Wiring Economy and Volume Exclusion Determine Neuronal Placement in the Drosophila Brain , 2011, Current Biology.

[47]  F. Pichaud,et al.  Immunofluorescent staining and imaging of the pupal and adult Drosophila visual system , 2007, Nature Protocols.

[48]  D. Baker,et al.  A Double S Shape Provides the Structural Basis for the Extraordinary Binding Specificity of Dscam Isoforms , 2008, Cell.

[49]  Benjamin H. White,et al.  A conditional tissue-specific transgene expression system using inducible GAL4 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Sperry.  CHEMOAFFINITY IN THE ORDERLY GROWTH OF NERVE FIBER PATTERNS AND CONNECTIONS. , 1963, Proceedings of the National Academy of Sciences of the United States of America.

[51]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[52]  M J Bastiani,et al.  Cell recognition during neuronal development. , 1984, Science.

[53]  F. Diao,et al.  A Hard-Wired Glutamatergic Circuit Pools and Relays UV Signals to Mediate Spectral Preference in Drosophila , 2014, Neuron.