@article {49529, title = {Neuron-subtype-specific expression, interaction affinities, and specificity determinants of DIP/Dpr cell recognition proteins.}, journal = {Neuron}, volume = {100}, year = {2018}, month = {2018 Nov 12}, pages = {1385-1400}, abstract = {

Binding between DIP and Dpr neuronal recognition proteins has been proposed to regulate synaptic connections between lamina and medulla neurons in the Drosophila visual system. Each lamina neuron was previously shown to express many Dprs. Here, we demonstrate, by contrast, that their synaptic partners typically express one or two DIPs, with binding specificities matched to the lamina neuron-expressed Dprs. A deeper understanding of the molecular logic of DIP/Dpr interaction requires quantitative studies on the properties of these proteins. We thus generated a quantitative affinity-based DIP/Dpr interactome for all DIP/Dpr protein family members. This revealed a broad range of affinities and identified homophilic binding for some DIPs and some Dprs. These data, along with full-length ectodomain DIP/Dpr and DIP/DIP crystal structures, led to the identification of molecular determinants of DIP/Dpr specificity. This structural knowledge, along with a comprehensive set of quantitative binding affinities, provides new tools for functional studies in\ vivo.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2018.10.046}, author = {Cosmanescu, Filip and Katsamba, Phinikoula S and Sergeeva, Alina P and Ahlsen, Goran and Patel, Saurabh D and Brewer, Joshua J and Tan, Liming and Xu, Shuwa and Xiao, Qi and Nagarkar-Jaiswal, Sonal and Nern, Aljoscha and Bellen, Hugo J and Zipursky, S Lawrence and Honig, Barry and Shapiro, Lawrence} } @article {47237, title = {Ig superfamily ligand and receptor pairs expressed in synaptic partners in Drosophila.}, journal = {Cell}, volume = {163}, year = {2015}, month = {2015 Dec 17}, pages = {1756-69}, abstract = {

Information processing relies on precise patterns of synapses between neurons. The cellular recognition mechanisms regulating this specificity are poorly understood. In the medulla of the Drosophila visual system, different neurons form synaptic connections in different layers. Here, we sought to identify candidate cell recognition molecules underlying this specificity. Using RNA sequencing (RNA-seq), we show that neurons with different synaptic specificities express unique combinations of mRNAs encoding hundreds of cell surface and secreted proteins. Using RNA-seq and protein tagging, we demonstrate that 21 paralogs of the Dpr family, a subclass of immunoglobulin (Ig)-domain containing proteins, are expressed in unique combinations in homologous neurons with different layer-specific synaptic connections. Dpr interacting proteins (DIPs), comprising nine paralogs of another subclass of Ig-containing proteins, are expressed in a complementary layer-specific fashion in a subset of synaptic partners. We propose that pairs of Dpr/DIP paralogs contribute to layer-specific patterns of synaptic connectivity.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2015.11.021}, author = {Tan, Liming and Zhang, Kelvin Xi and Pecot, Matthew Y and Nagarkar-Jaiswal, Sonal and Lee, Pei-Tseng and Takemura, Shin-ya and McEwen, Jason M and Nern, Aljoscha and Xu, Shuwa and Tadros, Wael and Chen, Zhenqing and Zinn, Kai and Bellen, Hugo J and Morey, Marta and Zipursky, S Lawrence} } @article {4156, title = {Genetic manipulation of genes and cells in the nervous system of the fruit fly.}, journal = {Neuron}, volume = {72}, year = {2011}, month = {2011 Oct 20}, pages = {202-30}, abstract = {

Research in the fruit fly Drosophila melanogaster has led to insights in neural development, axon guidance, ion channel function, synaptic transmission, learning and memory, diurnal rhythmicity, and neural disease that have had broad implications for neuroscience. Drosophila is currently the eukaryotic model organism that permits the most sophisticated in\ vivo manipulations to address the function of neurons and neuronally expressed genes. Here, we summarize many of the techniques that help assess the role of specific neurons by labeling, removing, or altering their activity. We also survey genetic manipulations to identify and characterize neural genes by mutation, overexpression, and protein labeling. Here, we attempt to acquaint the reader with available options and contexts to apply these methods.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2011.09.021}, author = {Venken, Koen J T and Simpson, Julie H and Bellen, Hugo J} } @article {2634, title = {Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling.}, journal = {Neuron}, volume = {63}, year = {2009}, month = {2009 Jul 30}, pages = {203-15}, abstract = {

Synaptic vesicle endocytosis is critical for maintaining synaptic communication during intense stimulation. Here we describe Tweek, a conserved protein that is required for synaptic vesicle recycling. tweek mutants show reduced FM1-43 uptake, cannot maintain release during intense stimulation, and harbor larger than normal synaptic vesicles, implicating it in vesicle recycling at the synapse. Interestingly, the levels of a fluorescent PI(4,5)P(2) reporter are reduced at tweek mutant synapses, and the probe is aberrantly localized during stimulation. In addition, various endocytic adaptors known to bind PI(4,5)P(2) are mislocalized and the defects in FM1-43 dye uptake and adaptor localization are partially suppressed by removing one copy of the phosphoinositide phosphatase synaptojanin, suggesting a role for Tweek in maintaining proper phosphoinositide levels at synapses. Our data implicate Tweek in regulating synaptic vesicle recycling via an action mediated at least in part by the regulation of PI(4,5)P(2) levels or availability at the synapse.

}, keywords = {Animals, Blotting, Complementary, Diptera, DNA, Drosophila Proteins, Electron, Endocytosis, Eye Abnormalities, Immunohistochemistry, Microscopy, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Neurons, Phosphatidylinositol Phosphates, Pyridinium Compounds, Quaternary Ammonium Compounds, Reverse Transcriptase Polymerase Chain Reaction, Synapses, Synaptic Transmission, Synaptic Vesicles, Transmission, Western}, issn = {1097-4199}, doi = {10.1016/j.neuron.2009.06.017}, author = {Verstreken, Patrik and Ohyama, Tomoko and Haueter, Claire and Habets, Ron L P and Lin, Yong Q and Swan, Laura E and Ly, Cindy V and Venken, Koen J T and De Camilli, Pietro and Bellen, Hugo J} } @article {2670, title = {Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles.}, journal = {The Journal of Cell Biology}, volume = {179}, year = {2007}, month = {2007 Dec 31}, pages = {1481-96}, abstract = {

Posttranslational modification through palmitoylation regulates protein localization and function. In this study, we identify a role for the Drosophila melanogaster palmitoyl transferase Huntingtin-interacting protein 14 (HIP14) in neurotransmitter release. hip14 mutants show exocytic defects at low frequency stimulation and a nearly complete loss of synaptic transmission at higher temperature. Interestingly, two exocytic components known to be palmitoylated, cysteine string protein (CSP) and SNAP25, are severely mislocalized at hip14 mutant synapses. Complementary DNA rescue and localization experiments indicate that HIP14 is required solely in the nervous system and is essential for presynaptic function. Biochemical studies indicate that HIP14 palmitoylates CSP and that CSP is not palmitoylated in hip14 mutants. Furthermore, the hip14 exocytic defects can be suppressed by targeting CSP to synaptic vesicles using a chimeric protein approach. Our data indicate that HIP14 controls neurotransmitter release by regulating the trafficking of CSP to synapses.

}, keywords = {Acyltransferases, Adaptor Proteins, Animals, Drosophila melanogaster, Drosophila Proteins, Exocytosis, Ganglia, Invertebrate, Nerve Tissue Proteins, Nervous System, Neuromuscular Junction, Neurotransmitter Agents, Post-Translational, Protein Processing, Protein Transport, Signal Transducing, Synaptic Transmission, Synaptic Vesicles}, issn = {1540-8140}, doi = {10.1083/jcb.200710061}, author = {Ohyama, Tomoko and Verstreken, Patrik and Ly, Cindy V and Rosenmund, Tanja and Rajan, Akhila and Tien, An-Chi and Haueter, Claire and Schulze, Karen L and Bellen, Hugo J} }