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.
© 2015 Elsevier. Received 23 April 2015, Revised 27 September 2015, Accepted 10 November 2015, Available online 17 December 2015. We thank Maximilien Courgeon, Claude Desplan, and Takashi Suzuki for advice on OL experiments, Takashi Suzuki for Rh4 > Brp-short^(mCherry), Chi-hon Lee for Dm8 and Tm5a/b GAL4 drivers, Elizabeth Gavis for UAS-CD4-tdTomato, and the Bloomington Drosophila Stock Center (BDSC) for other lines. We thank Larry Zipursky and Liming Tan for discussions and communication of data before publication. We thank Alexander Borst and Namrata Bali for discussions; Elena Armand, Suzanne Fischer, Deepa Waghray, and Kelsey Carter for technical assistance; and Violana Nesterova for help with Figure 5A. This work was supported by NIH RO1 grant NS62821 and R37 grant NS28182 to K.Z. and by the Howard Hughes Medical Institute (HHMI) (H.J.B. and K.C.G. labs). Stanford Synchrotron Radiation Lightsource beamlines 11-1 and 12-2 at SLAC National Accelerator Lab are supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences (DE-AC02-76SF00515). The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the NIH, NIGMS (including P41GM103393). Author Contributions: R.A.C. analyzed dpr and DIP expression and phenotypes in larvae. K.P.M. analyzed expression and phenotypes in the OL. E.Ö. and M.E.B. performed the structural studies. S.N.-J. and P-T.L. generated tagged MiMIC lines. M.J., E.Ö., and K.Z. generated the new Dpr-ome. K.Z., E.Ö., K.C.G., and H.B. analyzed data and supervised experiments. The accession number for the atomic coordinates and structure factors of the crystal structure reported in this paper is PDB: 5EO9.
Supplemental Material - mmc1.pdf
Accepted Version - nihms-743748.pdf