THESIS
2014
xiv, 86 pages : illustrations (some color) ; 30 cm
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 p...[
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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.
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