Cell Type-Specific Requirements for Heparan Sulfate Biosynthesis at the Drosophila Neuromuscular Junction: Effects on Synapse Function, Membrane Trafficking, and Mitochondrial Localization

• Published in: The Journal of neuroscience 2009-07, Vol.29 (26), p.8539-8550
• Main Authors: Ren, Yi, Kirkpatrick, Catherine A, Rawson, Joel M, Sun, Mu, Selleck, Scott B
• Format: Article
• Language: English
• Subjects: Animals; Animals, Genetically Modified; Behavior, Animal - physiology; Cell Communication - physiology; Cell Movement - genetics; Cell Movement - physiology; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Endocytosis - genetics; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Gene Expression Regulation - physiology; Green Fluorescent Proteins - genetics; Heparan Sulfate Proteoglycans - biosynthesis; Heparan Sulfate Proteoglycans - genetics; Heparan Sulfate Proteoglycans - metabolism; Heparitin Sulfate - biosynthesis; Heparitin Sulfate - genetics; Horseradish Peroxidase - metabolism; Larva; Locomotion - physiology; Microscopy, Electron, Transmission - methods; Mitochondria - metabolism; Mitochondria - ultrastructure; Muscle, Skeletal - metabolism; Muscle, Skeletal - ultrastructure; Mutation; Neuromuscular Junction - cytology; Neuromuscular Junction - physiology; Neuromuscular Junction - ultrastructure; Neurons - classification; Neurons - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.5587-08.2009

Heparan sulfate proteoglycans (HSPGs) are concentrated at neuromuscular synapses in many species, including Drosophila. We have established the physiological and patterning functions of HSPGs at the Drosophila neuromuscular junction by using mutations that block heparan sulfate synthesis or sulfation to compromise HSPG function. The mutant animals showed defects in synaptic physiology and morphology suggesting that HSPGs function both presynaptically and postsynaptically; these defects could be rescued by appropriate transgene expression. Of particular interest were selective disruptions of mitochondrial localization, abnormal distributions of Golgi and endoplasmic reticulum markers in the muscle, and a markedly increased level of stimulus-dependent endocytosis in the motoneuron. Our data support the emerging view that HSPG functions are not limited to the cell surface and matrix environments, but also affect a diverse set of cellular processes including membrane trafficking and organelle distributions.