mBDNF and proBDNF regulation of GABA neurotransmission (WP4829)
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].
Discuss this pathway
Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.
Pathway Ontologybrain-derived neurotrophic factor signaling pathway
- Constitutive endocytosis of GABAA receptors by an association with the adaptin AP2 complex modulates inhibitory synaptic currents in hippocampal neurons. Kittler JT, Delmas P, Jovanovic JN, Brown DA, Smart TG, Moss SJ. J Neurosci. 2000 Nov 1;20(21):7972–7. PubMed Europe PMC Scholia
- Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and Disease Brains. Porcher C, Medina I, Gaiarsa JL. Front Cell Neurosci. 2018 Aug 28;12:273. PubMed Europe PMC Scholia