A preliminary characterization of neuroligin interacting proteins

Abstract

Neuroligins are cell adhesion molecules on the postsynaptic membrane that associate with their presynaptic partners, neurexins. The trans-synaptic neuroligin-neurexin interaction has been extensively investigated in the central nervous system for their functions in synapse formation and function. Mutations in NLGN gene are known to be associated with autism spectrum disorders. Neuroligin deletion mutant mice displayed impaired synaptic transmission and neuronal network activity. In vitro co-culture assay showed that neuroligin presented by non-neuronal cell was sufficient to trigger presynaptic specification while neurexin was sufficient to trigger postsynaptic specification. Nonetheless, the molecular mechanisms on how simple trans-synaptic interaction drives a near-complete program for synaptic differentiation and how NLGN mutations disrupt synaptic function and the normal neurological development are still unknown. In this study, we identified two neuroligin interacting proteins. These two neuroligin interacting proteins co-localized with neuroligin 1 and neuroligin 3 but did not co-localize with neuroligin 2 in neurons. In parallel, they co-localized with excitatory postsynaptic marker PSD-95 but did not co-localize with inhibitory postsynaptic marker gephyrin. These results imply their specific functions at the excitatory synapse. With a series of deletion mutants, we also identified the critical regions which were responsible for their interaction with neuroligin or their synaptic localization. Further studies to elucidate the functions of these two neuroligin interacting proteins at synapse and the underlying molecular mechanisms may provide better understanding of the novel functions of neuroligins and related diseases.

Date of Award	2014
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology