mBDNF and proBDNF regulation of GABA neurotransmission (Homo sapiens)

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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 Porcher et al.