WP4829 - mBDNF and proBDNF regulation of GABA neurotransmission - Homo sapiens

This pathway depicts the regulation of GABA receptor surface expression of BDNF signaling.
BDNF can be secreted in both a mature form (mBDNF) and a precursor form (proBDNF), both of which modulate GABA synaptic transmission in neurons.

mBDNF activates TrkB receptors leading to an inhibition of GABAAR endocytosis and a consequent increase in cell surface expression of these receptors through the PI 3-kinase and the PKC signaling pathway. In addition, BDNF/TrkB signaling regulates GABAAR and KCC2 at the transcriptional level through the Shc, PLCg and MAP/ERK pathways.
proBDNF activates NGFR, which decreases GABAARs cell surface expression through the RhoA/ROCK/PTEN pathway, through dephosphorylation of GABAAR followed by endocytosis and degradation of internalized receptors. proBNDF/NGFR signaling also leads to the transcriptional repression of GABAAR synthesis through JAK2/STAT3/CREM. The proBDNF/NGFR signaling also decreases KCC2 expression.

This pathway is based on figure 1 from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6121065/ Porcher et al].