Figure 2.

BDNF processing, packaging and secretion in neurons. BDNF is synthesized as a pre-proBDNF protein, which has its pre-sequence cleaved off in the endoplasmic reticulum (ER). The resulting 32-kDa proBDNF moves, via the Golgi apparatus, into the trans-Golgi network (TGN) where two kinds of secretory vesicles are generated: those of the constitutive secretory pathway and those of the regulated pathway, whose secretion is activity-dependent. ProBDNF packaged in both types of vesicles is either proteolytically cleaved and secreted as 14-kDa mBDNF, or secreted as proBDNF and cleaved by extracellular proteases. The extent of the intra and extracellular processing of proBDNF is not exactly clear, but secretion of the proBDNF predominates. Both proBDNF and mBDNF are preferentially packaged into vesicles of the regulated secretory pathway. Once released, proBDNF binds preferentially to pan neurotrophin receptor p75^NTR and mBDNF binds preferentially to both pre-and post-synaptic TrkB receptors, activating different intracellular secondary messenger cascades and affecting distinct cellular responses.