Conformational Plasticity in a Transsynaptic Adhesion Complex
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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 Ozkan 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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