Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization
AS Yatsenko, MM Kucherenko, Y Xie, H Urlaub… - Elife, 2021 - elifesciences.org
AS Yatsenko, MM Kucherenko, Y Xie, H Urlaub, HR Shcherbata
Elife, 2021•elifesciences.orgTo 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
lissencephaly was used to understand how Dg is regulated in the brain. During …
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
lissencephaly was used to understand how Dg is regulated in the brain. During …
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 lissencephaly 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.
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