Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

Author:

Yatsenko Andriy S1,Kucherenko Mariya M2,Xie Yuanbin2,Urlaub Henning34,Shcherbata Halyna R12ORCID

Affiliation:

1. Institute of Cell Biochemistry, Hannover Medical School, Hannover, Germany

2. Max Planck Research Group of Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

3. Bioanalytical Mass Spectrometry Research Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany

4. University Medical Center Göttingen, Bioanalytics, Institute for Clinical Chemistry, Göttingen, Germany

Abstract

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 establishedDrosophilamodel 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.

Funder

EMBO

VolkswagenStiftung

Behrens-Weise-Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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