APP Has a Role in Synaptic Development
In today's Journal of Neuroscience, Vivian Budnik, Laura Torroja, and their colleagues at the University of Massachusetts, Amherst, and Brandeis University, Massachusetts, provide evidence that under normal circumstances, APP is a critical player in the formation and maintenance of synapses.
Using Drosophila mutants that over- or underexpress the APP homolog APPL, the researchers described the pattern of APPL transport to motor axons. Overexpression of APPL led to dramatic increases in synaptic boutons and to changes in synapse structure, whereas underexpression of APPL led to decreases in bouton numbers. Using selective deletion of portions of APPL, the researchers were also able to identify a cytoplasmic domain (at a putative G protein binding site) essential for the protein's activity at synapses. Finally, using a mutant with hyperexcitable neurons, the researchers were able to show that APPL activity at synapses is regulated by neuronal activity.
Based on the finding that APPL's actions at synapses depend on a putative signal transduction site, and the fact that neuronal activity regulates this action, the authors suggest that APPL plays a critical role in regulating the size of synaptic arbors.—Hakon Heimer
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- Torroja L, Packard M, Gorczyca M, White K, Budnik V. The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J Neurosci. 1999 Sep 15;19(18):7793-803. PubMed.
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Mount Sinai School of Medicine, NYU
This is an important finding as it suggests that APP may also have a role in synaptic structure or function. We should remember that AD is probably a synaptic disorder.View all comments by Nikolaos K. Robakis
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