Conformational Plasticity in a Transsynaptic Adhesion Complex

The figure shows a model where neurexin (Nrxn1a) of a PF interacts via specific regions (SS4, CRN) with cerebellin (Cbln1) to complex a delta-type glutamate receptor (GluD2) of a Purkinje neuron.

Engin Özkan group (University of Chicago)


Specific cell-cell interactions are also critical to brain function, which depends on the proper wiring of neurons through synapses, and their maintenance, regulation and elimination. The group of Engin Özkan at the University of Chicago elucidated a structural model for a large protein complex that brings together two types of neurons and is implicated in synapse formation and plasticity in the cerebellum, which is responsible for motor coordination and fine movement. Numerous Parallel Fibers (PF) of granule cells deep in the cerebellum cortex form excitatory synapses onto dendrites of Purkinje cells, which are large inhibitory neurons also in the cerebellum. Neurexins (Nxrns) are cell adhesion molecules in pre-synaptic terminals of PFs that can exist in > 1,000 forms for a given Nxrn gene, due to use of different start and splice sites. Nxrns can bind to delta-type glutamate receptors (GluD) on post-synaptic terminals of Purkinje cells via an intermediary protein called cerebellin. Crystal structures of components were determined, which enabled the researchers to construct a model of the neurexin-cerebellin-glutamate receptor complex. This study provides an example of the complicated structural architecture of an alternative splicing-dependent complex made up of 18 subunits, with extensive flexibility and large conformational changes that likely affect downstream neuronal function. The molecular structure also revealed how this complex can bridge the entire 20-25-nm span of the synaptic cleft.


Cheng S, Seven AB, Wang J, Skiniotis G, Özkan E, "Conformational Plasticity in the Transsynaptic Neurexin-Cerebellin-Glutamate Receptor Adhesion Complex," Structure 24 (12), 2163-2173 (2016). DOI: 10.1016/j.str.2016.11.004



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