Neurotrophins: A Ticket to Ride for BDNF

Kerrie Thomas, Alun Davies
2005 Current Biology  
Activity-dependent modulation of synapses is critical for brain development and for many cognitive functions in the mature brain. Amongst the neurotrophins, BDNF has for a unique role in long-term potentiation, a form of synaptic plasticity associated with memory formation, and the consolidation of long-term memory [1,2]. Over the past decade it has been established that neuronal activity regulates bdnf transcription, transport of BDNF mRNA and protein into neuronal processes and
more » ... nt secretion of BDNF to modulate synaptic transmission and synaptogenesis [3-7]. Little, however, is known about the mechanisms that mediate these processes. A recent study by Lou et al. [8] highlights the importance of the interaction of a highly conformation-dependent sorting signal in the tertiary structure of BDNF with the sorting receptor carboxypeptidase E [9] for segregating BDNF into the regulated secretory pathway for activity-dependent release. Secreted proteins transit the Golgi apparatus to the trans-Golgi network where two kinds of secretory vesicle are generated: those of the constitutive pathway are transported to and fuse with the plasma membrane to continuously release their contents into the extracellular space, whereas those of the regulated pathway migrate to and accumulate at the plasma membrane until fusion is triggered by signals for regulated secretion. Neurotrophins are synthesized from large precursor proteins that are proteolytically cleaved either
doi:10.1016/j.cub.2005.03.023 pmid:15823529 fatcat:3jeoush33jchvc44u7kvam3r6q