Author: Shannon Brown
Mentor: Dr. Joanna I. Giza
Institution: BMCC
Abstract: Everything we remember is encoded as plastic changes at small protrusions called spines, located on the dendritic branches of nerve cells. A molecule implicated in governing these changes, brain-derived neurotrophic factor (BDNF), binds to TrkB, a post-synaptic receptor for BDNF, and is internalized, mediating spine head diameter and synaptic plasticity. BDNF is synthesized in an immature form containing a prodomain, which is subsequently cleaved, yielding functional BDNF and an independent prodomain, which was thought to have no biological function. Giza et al. (Neuron, 2018) found that the independent prodomain is a biologically active molecule that shrinks spines and eliminates synapses in neurons. Additionally, Giza et al. found that a single polymorphism, changing Valine (Val) at position 66 to Methionine (Met), present in 30% of the population, predisposes carriers to neuropsychiatric disorders with underlying effects on synaptic plasticity, including Alzheimer’s and PTSD. Here, using super-resolution microscopy 3D SIM, we show that mature BDNF and Met prodomain exist as separate molecules and in complexes at the level of the dendritic spine. Further, the presence of the Met prodomain abolishes the effect of BDNF on spines. We hypothesize that the BDNF-Met complex interferes with BDNF-TrkB signaling by abolishing BDNF-TrkB internalization and signaling at the spine, and possibly recruiting other pro-shrinkage proteins into a complex with BDNF and TrkB.
BDNF Met Prodomain Changes BDNF Signaling
