Neuronal dystroglycan interactome

To assemble a brain, differentiating neurons must make proper connections
and establish specialized brain compartments. Abnormal levels of cell
adhesion molecules disrupt these processes. Dystroglycan (Dg) is a major
non-integrin cell adhesion receptor, deregulation of which is associated
with dramatic neuroanatomical defects such as lissencephaly type II, or
cobblestone brain. The previously
established Drosophila model for cobblestone encephaly
was used to understand how Dg is regulated in the brain. During
development, Dg has a spatiotemporally dynamic expression pattern,
fine-tuning of which is crucial for accurate brain assembly. In addition,
mass spectrometry analyses identified numerous components associated with
Dg in neurons, including several proteins of the exocyst
complex. Data show that exocyst-based membrane
trafficking of Dg allows its distinct expression pattern, essential for
proper brain morphogenesis. Further studies of the Dg neuronal interactome
will allow identification of new factors involved in the development of
dystroglycanopathies and advance disease diagnostics in humans.