Our laboratory is particularly fascinated by the complex protein
networks in the synaptic cleft found at chemical synapses, i.e. the
250 space between the 'pre-synaptic' membrane which hosts the
exocytosis machinery for synaptic vesicles and the 'post-synaptic'
membrane which hosts machinery responding to the transmitted chemical
signals. We are studying a number of synaptic adhesion molecules and
synaptic organizers to understand their role in mediating synapse
formation, maintenance, and plasticity. One family of synaptic adhesion
molecules that we have studied extensively is the family of neurexins.
Neurexins play a role in synapse organization and adhesion. Mutations
and lesions in neurexins have recently been implicated in autism
spectrum disorder, schizophrenia and mental retardation. Excitingly,
not only neurexins, but also many of their direct protein partners in
the synaptic cleft are implicated in these diseases as well (Fig. 1).
Neurexins and their partners must touch fundamental biological processes
that are involved in the pathogenesis of these disorders, but it is not
clear which processes these are and the exact role that neurexins and
their partners play in these processes.
Our laboratory is working to understand on a molecular level how
neurexins, their partners, as well as a number of other synaptic
organizers recognize, bind, and arrange different synaptic partners in
the synaptic cleft impacting synaptic function. By understanding the
molecular mechanisms of these molecules, we will be able to not only
further delineate their role at synapses but also understand why these
molecules, when disrupted, contribute to neurological disorders.
We use biochemical and biophysical techniques as well as protein crystallography (Fig. 2).