ADDUCIN REGULATES THE NEUROMUSCULAR JUNCTION IN DROSOPHILA

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Nerve cells communicate with one another at junctions termed synapses; when a neuron connects to muscle, the connecting synapse is called a neuromuscular junction (NMJ). The NMJ is similar but not identical to synapses between neurons and can can serve as a model for synapses in general. We have found that a protein called Adducin (Add) is located at the NMJ of the fruit fly. Others have found that this protein is present in synapses in the mammalian brain. Knowledge about the function of this protein at the fruit fly NMJ can help us understand how synapses in the brain work, which could also clarify how memory and learning occur. We have also found that levels of Adducin (called Hts in the fly) can increase or decrease the size of the synaptic branching at the NMJ. This is important as the synaptic branching is likely involved in modifying a 'motor memory', or may serve as a way of changing the efficiency of information transfer from a neuron to a muscle so as to enhance motor performance precision. To understand how Adducin achieves its effects we will see what other proteins it interacts with. We find that Adducin/Hts is closely linked to another protein called Discs large (Dlg), which is similar in structure to an important protein in mammalian synapses called the PSD-95 protein. Interestingly, the Adducin/Hts protein can modify the Dlg protein through the action of several enzymes called protein kinases and we think that Add/Hts is acting through these protein kinases to modify Dlg. In this grant we will explore how much of the effects of Adducin/Hts is mediated by acting on Dlg. We will also explore other ways of how Adducin/Hts may be acting even if its effects are not mediated by Dlg. For instance, Adducin/Hts may be sticking to the membranes of cells and acting as a scaffold to permit binding of the cellular 'skeleton' of actin and spectrin filaments that are important for the structure of the synapse. The Adducin/Hts protein may be acting as a switch to change the synapse from being in a stable functioning state, or in a state where the synapse will grow or shrink, and increase or decrease its efficiency in information transmission.