RT Journal Article SR Electronic T1 The Drosophila β-Amyloid Precursor Protein Homolog Promotes Synapse Differentiation at the Neuromuscular Junction JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7793 OP 7803 DO 10.1523/JNEUROSCI.19-18-07793.1999 VO 19 IS 18 A1 Laura Torroja A1 Mary Packard A1 Michael Gorczyca A1 Kalpana White A1 Vivian Budnik YR 1999 UL http://www.jneurosci.org/content/19/18/7793.abstract AB Although abnormal processing of β-amyloid precursor protein (APP) has been implicated in the pathogenic cascade leading to Alzheimer’s disease, the normal function of this protein is poorly understood. To gain insight into APP function, we used a molecular-genetic approach to manipulate the structure and levels of the DrosophilaAPP homolog APPL. Wild-type and mutant forms of APPL were expressed in motoneurons to determine the effect of APPL at the neuromuscular junction (NMJ). We show that APPL was transported to motor axons and that its overexpression caused a dramatic increase in synaptic bouton number and changes in synapse structure. In anAppl null mutant, a decrease in the number of boutons was found. Examination of NMJs in larvae overexpressing APPL revealed that the extra boutons had normal synaptic components and thus were likely to form functional synaptic contacts. Deletion analysis demonstrated that APPL sequences responsible for synaptic alteration reside in the cytoplasmic domain, at the internalization sequence GYENPTY and a putative Go-protein binding site. To determine the likely mechanisms underlying APPL-dependent synapse formation, hyperexcitable mutants, which also alter synaptic growth at the NMJ, were examined. These mutants with elevated neuronal activity changed the distribution of APPL at synapses and partially suppressed APPL-dependent synapse formation. We propose a model by which APPL, in conjunction with activity-dependent mechanisms, regulates synaptic structure and number.