APBBs

APBBs, or APBB proteins, are a small family of adaptor proteins that bind to the intracellular tail of amyloid precursor protein (APP) and other NPXY-containing receptors through their phosphotyrosine-binding (PTB) domains. In humans the family includes APBB1 (Fe65), APBB2 (Fe65-like 1), and APBB3 (Fe65-like 2). These proteins function as scaffolds that link membrane receptor signaling to intracellular responses, influencing endocytosis, trafficking, and transcription.

In APP biology, APBB proteins form complexes with APP’s intracellular domain (AICD) and with nuclear co-factors such as Tip60, promoting the nuclear translocation of AICD and regulation of target gene expression. Through these interactions, APBBs can couple membrane events to changes in transcriptional programs, which has implications for neuronal development and synaptic function. APBBs are widely expressed, with notable enrichment in the brain, where they participate in neural signaling networks.

Dysregulation of APBB function or APP-APBB interactions has been explored in the context of Alzheimer’s disease models, where alterations in APP processing and Aβ production may be influenced by adaptor protein activity and receptor trafficking. Beyond APP, APBB family members can bind other NPXY-containing receptors, reflecting a broader role in coordinating signaling and cellular trafficking.

APBB proteins are evolutionarily conserved across vertebrates and, in some cases, other organisms, underscoring their fundamental role as adaptor proteins in multiple signaling pathways. In summary, APBBs are versatile components that connect membrane receptor signaling to transcriptional responses, with particular relevance to APP biology and neural function.