scholarly journals Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Shouqiang Cheng ◽  
James Ashley ◽  
Justyna D Kurleto ◽  
Meike Lobb-Rabe ◽  
Yeonhee Jenny Park ◽  
...  
Keyword(s):  
Axon Guidance ◽  
Molecular Basis ◽  
Surface Proteins ◽  
Synaptic Connectivity ◽  
Immunoglobulin Superfamily ◽  
Neuronal Connectivity ◽  
Cell Surface Proteins ◽  
Synaptic Specificity ◽  
Immunoglobulin Superfamily Proteins ◽  
Synapse Targeting

In stereotyped neuronal networks, synaptic connectivity is dictated by cell surface proteins, which assign unique identities to neurons, and physically mediate axon guidance and synapse targeting. We recently identified two groups of immunoglobulin superfamily proteins in Drosophila, Dprs and DIPs, as strong candidates for synapse targeting functions. Here, we uncover the molecular basis of specificity in Dpr–DIP mediated cellular adhesions and neuronal connectivity. First, we present five crystal structures of Dpr–DIP and DIP–DIP complexes, highlighting the evolutionary and structural origins of diversification in Dpr and DIP proteins and their interactions. We further show that structures can be used to rationally engineer receptors with novel specificities or modified affinities, which can be used to study specific circuits that require Dpr–DIP interactions to help establish connectivity. We investigate one pair, engineered Dpr10 and DIP-α, for function in the neuromuscular circuit in flies, and reveal roles for homophilic and heterophilic binding in wiring.

scholarly journals Modular transcriptional programs separately define axon and dendrite connectivity

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Yerbol Z Kurmangaliyev ◽  
Juyoun Yoo ◽  
Samuel A LoCascio ◽  
S Lawrence Zipursky
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Transcriptional Control ◽  
Surface Proteins ◽  
Synaptic Connectivity ◽  
Loss Of Function ◽  
Neuronal Connectivity ◽  
Cell Surface Proteins ◽  
Single Cell Rna Sequencing ◽  
Single Cell Profiling

Patterns of synaptic connectivity are remarkably precise and complex. Single-cell RNA sequencing has revealed a vast transcriptional diversity of neurons. Nevertheless, a clear logic underlying the transcriptional control of neuronal connectivity has yet to emerge. Here, we focused on Drosophila T4/T5 neurons, a class of closely related neuronal subtypes with different wiring patterns. Eight subtypes of T4/T5 neurons are defined by combinations of two patterns of dendritic inputs and four patterns of axonal outputs. Single-cell profiling during development revealed distinct transcriptional programs defining each dendrite and axon wiring pattern. These programs were defined by the expression of a few transcription factors and different combinations of cell surface proteins. Gain and loss of function studies provide evidence for independent control of different wiring features. We propose that modular transcriptional programs for distinct wiring features are assembled in different combinations to generate diverse patterns of neuronal connectivity.

scholarly journals Modular transcriptional programs separately define axon and dendrite connectivity

2019 ◽  
Author(s):  
Yerbol Z. Kurmangaliyev ◽  
Juyoun Yoo ◽  
Samuel A. LoCascio ◽  
S. Lawrence Zipursky
Keyword(s):  
Transcription Factors ◽  
Single Cell ◽  
Transcriptional Control ◽  
Surface Proteins ◽  
Synaptic Connectivity ◽  
Loss Of Function ◽  
Neuronal Connectivity ◽  
Cell Surface Proteins ◽  
Single Cell Rna Sequencing ◽  
Single Cell Profiling

AbstractPatterns of synaptic connectivity are remarkably precise and complex. Single-cell RNA sequencing has revealed a vast transcriptional diversity of neurons. Nevertheless, a clear logic underlying the transcriptional control of neuronal connectivity has yet to emerge. Here, we focused on Drosophila T4/T5 neurons, a class of closely related neuronal subtypes with different wiring patterns. Eight subtypes of T4/T5 neurons are defined by combinations of two patterns of dendritic inputs and four patterns of axonal outputs. Single-cell profiling during development revealed distinct transcriptional programs defining each dendrite and axon wiring pattern. These programs were defined by the expression of a few transcription factors and different combinations of cell surface proteins. Gain and loss of function studies provide evidence for independent control of different wiring features. We propose that modular transcriptional programs for distinct wiring features are assembled in different combinations to generate diverse patterns of neuronal connectivity.

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

Cell ◽  
2015 ◽  
Vol 163 (7) ◽  
pp. 1770-1782 ◽  
Author(s):  
Robert A. Carrillo ◽  
Engin Özkan ◽  
Kaushiki P. Menon ◽  
Sonal Nagarkar-Jaiswal ◽  
Pei-Tseng Lee ◽  
...  
Keyword(s):  
Cell Surface ◽  
Surface Proteins ◽  
Synaptic Connectivity ◽  
Cell Surface Proteins

scholarly journals Author response: Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila

2018 ◽  
Author(s):  
Shouqiang Cheng ◽  
James Ashley ◽  
Justyna D Kurleto ◽  
Meike Lobb-Rabe ◽  
Yeonhee Jenny Park ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Author Response ◽  
Immunoglobulin Superfamily ◽  
Synaptic Specificity

scholarly journals R7 photoreceptor axon targeting requires matching levels of lost and found expression in R7 and its synaptic partners

2020 ◽  
Author(s):  
Jessica Douthit ◽  
Ariel Hairston ◽  
Gina Lee ◽  
Carolyn A. Morrison ◽  
Isabel Holguera ◽  
...  
Keyword(s):  
Cell Surface ◽  
Neural Circuits ◽  
Transmembrane Proteins ◽  
Surface Proteins ◽  
Cell Surface Proteins ◽  
Axon Targeting ◽  
Synaptic Specificity ◽  
Lost And Found ◽  
Intracellular Vesicles

AbstractThe formation of neural circuits requires growing processes to select the correct synaptic partners from numerous possible choices through interactions between cell surface proteins. The limited number of such proteins suggests that quantitative comparisons of their relative levels may contribute to synaptic specificity. Here we show that the level of the Drosophila CUB-LDL protein Lost and found (Loaf) in the UV-sensitive R7 photoreceptor relative to its synaptic partners is critical for R7 axon targeting. Although targeting occurs normally in loaf mutant animals, removing loaf from photoreceptors or restoring it to the postsynaptic neurons Tm5a/b or Dm9 in a loaf mutant causes mistargeting of R7 axons. Loaf localizes primarily to intracellular vesicles including endosomes. We propose that Loaf regulates the trafficking or function of one or more transmembrane proteins, and an excess of these proteins on the synaptic partners of R7 prevents the formation of stable connections.

What do nanometer molecular trajectories tell us about heterogeneous cell surface domaines?

1995 ◽  
Vol 53 ◽  
pp. 786-787
Author(s):  
Watt W. Webb
Keyword(s):  
Cell Surface ◽  
Lipid Membranes ◽  
Surface Proteins ◽  
Protein Diffusion ◽  
Coated Pits ◽  
Cell Surface Proteins ◽  
Membrane Heterogeneity ◽  
Fluorescence Photobleaching Recovery ◽  
Photobleaching Recovery ◽  
Plasma Membrane Heterogeneity

Plasma membrane heterogeneity is implicit in the existence of specialized cell surface organelles which are necessary for cellular function; coated pits, post and pre-synaptic terminals, microvillae, caveolae, tight junctions, focal contacts and endothelial polarization are examples. The persistence of these discrete molecular aggregates depends on localized restraint of the constituent molecules within specific domaines in the cell surface by strong intermolecular bonds and/or anchorage to extended cytoskeleton. The observed plasticity of many of organelles and the dynamical modulation of domaines induced by cellular signaling evidence evanescent intermolecular interactions even in conspicuous aggregates. There is also strong evidence that universal restraints on the mobility of cell surface proteins persist virtually everywhere in cell surfaces, not only in the discrete organelles. Diffusion of cell surface proteins is slowed by several orders of magnitude relative to corresponding protein diffusion coefficients in isolated lipid membranes as has been determined by various ensemble average methods of measurement such as fluorescence photobleaching recovery(FPR).

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