mBDNF and proBDNF regulation of GABA neurotransmission (Homo sapiens)

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1, 2NeuronNucleusEndocytosis??GABA gene expressionMAPKSTAT3AP2A1PKCRHOAPLCG1GABRA1proBDNFCREB1CREMSLC12A5NTRK2NGFRPTENPIK3CAPIK3CBPIK3R1PIK3R2PIK3R3PIK3CGAP2A2AP2B1SLC12A5mBDNFSLC12A5ROCK1JAK2?SHC1GABRA2GABRA3GABRA4GABRA5GABRA6GABRB1GABRB2GABRB3GABRG1GABRG2GABRG3GABRDGABREGABRPGABRQ


Description

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.

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Ontology Terms

 

Bibliography

  1. Kittler JT, Delmas P, Jovanovic JN, Brown DA, Smart TG, Moss SJ; ''Constitutive endocytosis of GABAA receptors by an association with the adaptin AP2 complex modulates inhibitory synaptic currents in hippocampal neurons.''; J Neurosci, 2000 PubMed Europe PMC
  2. Porcher C, Medina I, Gaiarsa JL; ''Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and Disease Brains.''; Front Cell Neurosci, 2018 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
109219view00:38, 28 February 2020KhanspersModified description
109218view00:34, 28 February 2020Khanspersupdated layout
109217view00:23, 28 February 2020KhanspersOntology Term : 'epilepsy' added !
109216view00:21, 28 February 2020KhanspersOntology Term : 'brain-derived neurotrophic factor signaling pathway' added !
109215view00:15, 28 February 2020KhanspersNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AP2A1GeneProductENSG00000196961 (Ensembl)
AP2A2GeneProductENSG00000183020 (Ensembl)
AP2B1GeneProductENSG00000006125 (Ensembl)
CREB1GeneProductENSG00000118260 (Ensembl)
CREMGeneProductENSG00000095794 (Ensembl)
GABRA1GeneProductENSG00000022355 (Ensembl)
GABRA2GeneProductENSG00000151834 (Ensembl)
GABRA3GeneProductENSG00000011677 (Ensembl)
GABRA4GeneProductENSG00000109158 (Ensembl)
GABRA5GeneProductENSG00000186297 (Ensembl)
GABRA6GeneProductENSG00000145863 (Ensembl)
GABRB1GeneProductENSG00000163288 (Ensembl)
GABRB2GeneProductENSG00000145864 (Ensembl)
GABRB3GeneProductENSG00000166206 (Ensembl)
GABRDGeneProductENSG00000187730 (Ensembl)
GABREGeneProductENSG00000102287 (Ensembl)
GABRG1GeneProductENSG00000163285 (Ensembl)
GABRG2GeneProductENSG00000113327 (Ensembl)
GABRG3GeneProductENSG00000182256 (Ensembl)
GABRPGeneProductENSG00000094755 (Ensembl)
GABRQGeneProductENSG00000268089 (Ensembl)
JAK2GeneProductENSG00000096968 (Ensembl)
  • CAV2; caveolin 2
  • Homology Mapping from Mus musculus to Homo sapiens: Original ID = L:16452
MAPKPathwayWP382 (WikiPathways)
NGFRGeneProductENSG00000064300 (Ensembl)
NTRK2GeneProductENSG00000148053 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CGGeneProductENSG00000105851 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PKCGeneProduct
PLCG1GeneProductENSG00000124181 (Ensembl)
PTENGeneProductENSG00000171862 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl)
ROCK1GeneProductENSG00000067900 (Ensembl)
SHC1GeneProductENSG00000160691 (Ensembl)
SLC12A5GeneProductENSG00000124140 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
mBDNFGeneProductENSG00000176697 (Ensembl)
proBDNFGeneProductENSG00000176697 (Ensembl)

Annotated Interactions

No annotated interactions

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