Drosophila Dscam Is an Axon Guidance Receptor Exhibiting Extraordinary Molecular Diversity

@article{Schmucker2000DrosophilaDI,
  title={Drosophila Dscam Is an Axon Guidance Receptor Exhibiting Extraordinary Molecular Diversity},
  author={Dietmar Schmucker and James C. Clemens and Huidy Shu and Carolyn A. Worby and Jian Xiao and Marco Muda and Jack E. Dixon and S. Lawrence Zipursky},
  journal={Cell},
  year={2000},
  volume={101},
  pages={671-684}
}
A Drosophila homolog of human Down syndrome cell adhesion molecule (DSCAM), an immunoglobulin superfamily member, was isolated by its affinity to Dock, an SH3/SH2 adaptor protein required for axon guidance. Dscam binds directly to both Dock's SH2 and SH3 domains. Genetic studies revealed that Dscam, Dock and Pak, a serine/threonine kinase, act together to direct pathfinding of Bolwig's nerve, containing a subclass of sensory axons, to an intermediate target in the embryo. Dscam also is required… 
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Analysis of Dscam Diversity in Regulating Axon Guidance in Drosophila Mushroom Bodies
TLDR
It is proposed that different extracellular domains of Dscam share a common function and that differences in isoforms expressed on the surface of neighboring axons influence interactions between them.
Got diversity? Wiring the fly brain with Dscam.
TLDR
Alternative splicing of Dscam mRNA potentially generates 38016 isoforms of a cell-surface recognition protein of the immunoglobulin superfamily, raising the intriguing possibility that specificity of binding by the D scam isoforms mediates cell- surface recognition events required for wiring the fly brain.
Alternative Splicing of Drosophila Dscam Generates Axon Guidance Receptors that Exhibit Isoform-Specific Homophilic Binding
TLDR
It is demonstrated that different isoforms exhibit different binding specificity, and it is proposed that this preferential homophilic binding specificity regulates interactions between cells and contributes to the formation of complex patterns of neuronal connections.
Dscam diversity is essential for neuronal wiring and self-recognition
TLDR
It is concluded that Dscam diversity provides each neuron with a unique identity by which it can distinguish its own processes from those of other neurons, and that this self-recognition is essential for wiring the Drosophila brain.
Cell-intrinsic requirement of Dscam1 isoform diversity for axon collateral formation
TLDR
It is proposed that the ratio of matching to nonmatching isoforms within a cell influences the Dscam1-mediated signaling strength, which in turn controls axon growth and growth cone sprouting.
The Molecular Diversity of Dscam Is Functionally Required for Neuronal Wiring Specificity in Drosophila
TLDR
The role of Dscam in neuron-target recognition of single mechanosensory neurons, which connect with different target cells through multiple axonal branches, is examined and a very large number of structurally unique receptor isoforms is required to ensure fidelity and precision of neuronal connectivity.
Slit and Receptor Tyrosine Phosphatase 69D Confer Spatial Specificity to Axon Branching via Dscam1
TLDR
It is reported that cell-autonomous loss of the receptor tyrosine phosphatase 69D (RPTP69D) and loss of midline-localized Slit inhibit formation of specific axon collaterals through modulation of Dscam1 activity, enabling the spatial specificity of axon collateral formation.
Drosophila Vap-33 Is Required for Axonal Localization of Dscam Isoforms
TLDR
It is proposed that Vap function is required in neurons to selectively traffic proteins to axons, and disruption of this function may contribute to the pathology of ALS.
The Down Syndrome Cell Adhesion Molecule
The Down syndrome cell adhesion molecules (DSCAMs) are a structurally and functionally conserved family of cell surface receptors that play important roles in nervous system organization. These…
Dscam and DSCAM: complex genes in simple animals, complex animals yet simple genes.
TLDR
How an unprecedented expansion of complex alternative splicing has been uniquely employed by arthropods to generate diverse surface receptors, important for cell-cell communication, molecular self-recognition in neurons, and innate immune defenses is discussed.
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    Proceedings of the National Academy of Sciences of the United States of America
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