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

  1. Andriy S Yatsenko
  2. Mariya M Kucherenko
  3. Yuanbin Xie
  4. Henning Urlaub
  5. Halyna R Shcherbata  Is a corresponding author
  1. Hannover Medical School, Germany
  2. Charite Medicine University, Germany
  3. Gannan Medical University, China
  4. University Medical Center 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 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.

Data availability

The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files or found on the Dryad Digital Repository (Data DOI: doi:10.5061/dryad.8sf7m0cmf).

The following data sets were generated

Article and author information

Author details

  1. Andriy S Yatsenko

    Institute of Cell Biochemistry, Hannover Medical School, Hannover, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Mariya M Kucherenko

    Institute of Physiology, Charite Medicine University, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Yuanbin Xie

    Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Gannan Medical University, Ganzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Henning Urlaub

    Bioanalytics, Institute of Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Halyna R Shcherbata

    Institute of Cell Biochemistry, Hannover Medical School, Hannover, Germany
    For correspondence
    halyna.shcherbata@mpibpc.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3855-0345

Funding

EMBO (YIP)

  • Halyna R Shcherbata

VW Stiftung (AZN3008)

  • Halyna R Shcherbata

Hannover Medical School

  • Halyna R Shcherbata

VW Stiftung (AZ97750)

  • Halyna R Shcherbata

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2021, Yatsenko et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,197
    views
  • 166
    downloads
  • 12
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Andriy S Yatsenko
  2. Mariya M Kucherenko
  3. Yuanbin Xie
  4. Henning Urlaub
  5. Halyna R Shcherbata
(2021)
Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization
eLife 10:e63868.
https://doi.org/10.7554/eLife.63868

Share this article

https://doi.org/10.7554/eLife.63868

Further reading

    1. Developmental Biology
    Mehmet Mahsum Kaplan, Erika Hudacova ... Ondrej Machon
    Research Article

    Hair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Using genetic approach in mice, we show that Meis2 expression in cells derived from the neural crest is critical for whisker formation and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factor Foxd1, which is typical of pre-dermal condensation. However, deletion of Foxd1 does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation or Foxd1 expression.

    1. Developmental Biology
    Bin Zhu, Rui Wei ... Pei Liang
    Research Article

    Wing dimorphism is a common phenomenon that plays key roles in the environmental adaptation of aphid; however, the signal transduction in response to environmental cues and the regulation mechanism related to this event remain unknown. Adenosine (A) to inosine (I) RNA editing is a post-transcriptional modification that extends transcriptome variety without altering the genome, playing essential roles in numerous biological and physiological processes. Here, we present a chromosome-level genome assembly of the rose-grain aphid Metopolophium dirhodum by using PacBio long HiFi reads and Hi-C technology. The final genome assembly for M. dirhodum is 447.8 Mb, with 98.50% of the assembled sequences anchored to nine chromosomes. The contig and scaffold N50 values are 7.82 and 37.54 Mb, respectively. A total of 18,003 protein-coding genes were predicted, of which 92.05% were functionally annotated. In addition, 11,678 A-to-I RNA-editing sites were systematically identified based on this assembled M. dirhodum genome, and two synonymous A-to-I RNA-editing sites on CYP18A1 were closely associated with transgenerational wing dimorphism induced by crowding. One of these A-to-I RNA-editing sites may prevent the binding of miR-3036-5p to CYP18A1, thus elevating CYP18A1 expression, decreasing 20E titer, and finally regulating the wing dimorphism of offspring. Meanwhile, crowding can also inhibit miR-3036-5p expression and further increase CYP18A1 abundance, resulting in winged offspring. These findings support that A-to-I RNA editing is a dynamic mechanism in the regulation of transgenerational wing dimorphism in aphids and would advance our understanding of the roles of RNA editing in environmental adaptability and phenotypic plasticity.