Understanding the interactions between GABAAR and synaptic adhesion proteins neuroligin1 And neuroligin2

Open Access
Khristov, Vladimir Rouskov
Area of Honors:
Bachelor of Science
Document Type:
Thesis Supervisors:
  • Bernhard Luscher, Thesis Supervisor
  • Gong Chen, Faculty Reader
  • Craig Eugene Cameron, Honors Advisor
  • Neurolign
  • GABA
  • Immunoprufication
  • Western
Gamma aminobutyric acid type A receptors (GABAARs) are the principal inhibitory receptors in the brain. Disruption of their function was shown to be a factor in familiar epilepsy and is further implicated in a number of other neurological and neuropsychiatric disorders. Of particular interest is the mechanism of trafficking and stabilization of GABAARs in the postsynaptic cell membrane. Preliminary findings in our lab had demonstrated that GABAAR subunits display differential interaction with different members of a family of synaptic adhesion molecules known as neuroligins (NLs). In this study, I went on to explore these interactions further, through analysis of modified NL constructs and the testing of additional GABAAR subunits. I observed efficientimmuno-copurification of GABAAR subunits and NLs from transfected human embryo kidney cells. Specifically, I found that the γ2 and β2 subunits interact stronger with NL2 than with NL1, while the α1 and α2 subunits show no preference for interaction with NL2 vs. NL1. Additionally, I observed some evidence of proteolytic degradation of NL2following coexpression specifically of the β3 subunit - no such effect was evident in the case of α1, 2 and the γ2 subunits. These results support the hypothesis that GABAARs and neuroligins corroborate in their postsynaptic targeting. It is possible that the interaction between γ2 and NL2 serves to stabilize specific subtypes of GABAARs at synaptic sites. However, the role of β3 in NL2 degradation has to be explored further and controlled for in future experiments.