Synthesis, trafficking and release of BDNF

Abstract

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays an important role in neuronal survival, differentiation, neurite outgrowth, spine formation, synaptic plasticity, and memory. The regulation of its biological activity is well controlled by its gene expression, axonal transport, and release. It is well known that BDNF is synthesized and released in an activity-dependent manner. However, the molecular mechanism for its processing, axonal transport, and release is still not completely understood. In our recent studies we found that Huntingtin-associated protein (HAP1) and sortilin play important roles in BDNF trafficking and processing. HAP1 plays critical roles in BDNF intracellular trafficking, dendritic targeting, and metabolism by binding to the prodomain of BDNF and forming a complex with sortilin. In this chapter, we focus on the recent progress made in understanding the molecular mechanism underlying the biosynthesis, transport, and release of BDNF, emphasizing the role of HAP1 and sortilin in the intracellular trafficking of BDNF.