FE65: Roles beyond amyloid precursor protein processing

: FE65 is a brain-enriched, developmentally regulated adaptor protein that was first identified as a binding partner of amyloid precursor protein (APP), an important molecule in Alzheimer's disease. FE65 possesses three protein interaction domains, including an N-terminal WW domain and two C-terminal phosphotyrosine-binding (PTB) domains. It is capable of mediating the assembly of multimolecular complexes. Although initial work reveals its roles in APP processing and gene transactivation, increasing evidence suggests that FE65 participates in more diverse biological processes than originally anticipated. This article discusses the role of FE65 in signal transduction during cell stress and protein turnover through the ubiquitin-proteasome system and in various neuronal processes, including neurogenesis, neuronal migration and positioning, neurite outgrowth, synapse formation and synaptic plasticity, learning, and memory.