The Extracellular and Cytoplasmic Domains of Syndecan Cooperate Postsynaptically to Promote Synapse Growth at the Drosophila Neuromuscular Junction.

The heparan sulfate proteoglycan (HSPG) Syndecan (Sdc) is a crucial regulator of synapse development and growth in both vertebrates and invertebrates. In Drosophila, Sdc binds via its extracellular heparan sulfate (HS) sidechains to the receptor protein tyrosine phosphatase LAR to promote the morphological growth of the neuromuscular junction (NMJ). To date, however, little else is known about the molecular mechanisms by which Sdc functions to promote synapse growth.

An extracellular interactome of immunoglobulin and LRR proteins reveals receptor-ligand networks.

Extracellular domains of cell surface receptors and ligands mediate cell-cell communication, adhesion, and initiation of signaling events, but most existing protein-protein "interactome" data sets lack information for extracellular interactions. We probed interactions between receptor extracellular domains, focusing on a set of 202 proteins composed of the Drosophila melanogaster immunoglobulin superfamily (IgSF), fibronectin type III (FnIII), and leucine-rich repeat (LRR) families, which are known to be important in neuronal and developmental functions. Out of 20,503 candidate protein pairs tested, we observed 106 interactions, 83 of which were previously unknown.

Electroretinograms in Drosophila: a robust and genetically accessible electrophysiological system for the undergraduate laboratory.

Laboratory courses in neurophysiology fulfill a critical need for inquiry-based training in undergraduate programs in neuroscience and biology. These courses typically use classical electrophysiological preparations to explore the basic features of neuronal function. However, current neuroscience research also focuses on elucidating the molecular and genetic mechanisms of neuronal function, using model systems that include mutant and transgenic animals.

Heparan sulfate proteoglycan specificity during axon pathway formation in the Drosophila embryo.

Axon guidance is influenced by the presence of heparan sulfate (HS) proteoglycans (HSPGs) on the surface of axons and growth cones (Hu, [2001]: Nat Neurosci 4:695-701; Irie et al. [2002]: Development 129:61-70; Inatani et al. [2003]: Science 302:1044-1046; Johnson et al.

LAR, liprin alpha and the regulation of active zone morphogenesis.

Active zones are protein-rich regions of neurons that act as sites of synaptic vesicle fusion and neurotransmitter release at the pre-synaptic terminus. Although the discovery that the receptor protein tyrosine phosphatase LAR and its cytoplasmic binding partner liprin alpha are essential for proper active zone formation is nearly a decade old, the underlying mechanisms are still poorly understood. Recent studies have identified a number of binding partners for both LAR and liprin alpha, several of which play key roles in active zone assembly.

The HSPGs Syndecan and Dallylike bind the receptor phosphatase LAR and exert distinct effects on synaptic development.

The formation and plasticity of synaptic connections rely on regulatory interactions between pre- and postsynaptic cells. We show that the Drosophila heparan sulfate proteoglycans (HSPGs) Syndecan (Sdc) and Dallylike (Dlp) are synaptic proteins necessary to control distinct aspects of synaptic biology. Sdc promotes the growth of presynaptic terminals, whereas Dlp regulates active zone form and function.

Heparan sulfate proteoglycans and the emergence of neuronal connectivity.

With the identification of the molecular determinants of neuronal connectivity, our understanding of the extracellular information that controls axon guidance and synapse formation has evolved from single factors towards the complexity that neurons face in a living organism. As we move in this direction - ready to see the forest for the trees - attention is returning to one of the most ancient regulators of cell-cell interaction: the extracellular matrix. Among many matrix components that influence neuronal connectivity, recent studies of the heparan sulfate proteoglycans suggest that these ancient molecules function as versatile extracellular scaffolds that both sculpt the landscape of extracellular cues and modulate the way that neurons perceive the world around them.

The heparan sulfate proteoglycans Dally-like and Syndecan have distinct functions in axon guidance and visual-system assembly in Drosophila.

Heparan sulfate proteoglycans (HSPGs), a class of glycosaminoglycan-modified proteins, control diverse patterning events via their regulation of growth-factor signaling and morphogen distribution. In C. elegans, zebrafish, and the mouse, heparan sulfate (HS) biosynthesis is required for normal axon guidance, and mutations affecting Syndecan (Sdc), a transmembrane HSPG, disrupt axon guidance in Drosophila embryos.

Axonal heparan sulfate proteoglycans regulate the distribution and efficiency of the repellent slit during midline axon guidance.

The presentation of secreted axon guidance factors plays a major role in shaping central nervous system (CNS) connectivity. Recent work suggests that heparan sulfate (HS) regulates guidance factor activity; however, the in vivo axon guidance roles of its carrier proteins (heparan sulfate proteoglycans, or HSPGs) are largely unknown. Here we demonstrate through genetic analysis in vivo that the HSPG Syndecan (Sdc) is critical for the fidelity of Slit repellent signaling at the midline of the Drosophila CNS, consistent with the localization of Sdc to CNS axons.

Receptor protein tyrosine phosphatases in nervous system development.

Receptor protein tyrosine phosphatases (RPTPs) are key regulators of neuronal morphogenesis in a variety of different vertebrate and invertebrate systems, yet the mechanisms by which these proteins regulate central nervous system development are poorly understood. In the past few years, studies have begun to outline possible models for RPTP function by demonstrating in vivo roles for RPTPs in axon outgrowth, guidance, and synaptogenesis. In addition, the crystal structures of several RPTPs have been solved, numerous downstream effectors of RPTP signaling have been identified, and a small number of RPTP ligands have been described.