Down syndrome cell adhesion molecule and its functions in neural development

The Down syndrome cell adhesion molecule (DSCAM) belongs to the immunoglobulin superfamily (IgSF) and plays important roles in neural development. It has a large ectodomain, including 10 Ig-like domains and 6 fibronectin III (FnIII) domains. Previous data have shown that DSCAM can mediate cell adhesion by forming homophilic dimers between cells and contributes to self-avoidance of neurites or neuronal tiling, which is important for neural network formation. However, the organization and assembly of DSCAM at cell adhesion interfaces has not been fully understood. Here we combine electron microscopy and other biophysical methods to characterize the structure of the DSCAM-mediated cell adhesion and generate three-dimensional views of the adhesion interfaces of DSCAM by electron tomography. The results show that mouse DSCAM forms a regular pattern at the adhesion interfaces. The Ig-like domains contribute to both trans homophilic interactions and cis assembly of the pattern, and the FnIII domains are crucial for the cis pattern formation as well as the interaction with the cell membrane. By contrast, no obvious assembly pattern is observed at the adhesion interfaces mediated by mouse DSCAML1 or Drosophila DSCAMs, suggesting the different structural roles and mechanisms of DSCAMs in mediating cell adhesion and neural network formation.

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Alternatively spliced down syndrome cell adhesion molecule (Dscam) controls innate immunity in crab

Journal of Biological Chemistry ◽

10.1074/jbc.ra119.010247 ◽

2019 ◽

Vol 294 (44) ◽

pp. 16440-16450 ◽

Cited By ~ 9

Author(s):

Dan Li ◽

Zhicheng Wan ◽

Xuejie Li ◽

Ming Duan ◽

Lei Yang ◽

...

Keyword(s):

Innate Immunity ◽

Down Syndrome ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Alternatively Spliced

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Herpes virus OsHV-1 and the protistPerkinsus marinusmodify the expression of the Down syndrome cell adhesion molecule gene in gill and mantle ofCrassostreaspp.

Aquaculture Research ◽

10.1111/are.13832 ◽

2018 ◽

Vol 49 (11) ◽

pp. 3638-3646 ◽

Cited By ~ 1

Author(s):

Lilián Arzeta-Pino ◽

Armando Acosta ◽

Maria E. Sarmiento ◽

Maurilia Rojas-Contreras ◽

Carmen Rodríguez-Jaramillo ◽

...

Keyword(s):

Down Syndrome ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Herpes Virus ◽

Adhesion Molecule Gene ◽

Herpès Virus

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Protein production, crystallization and preliminary crystallographic analysis of the four N-terminal immunoglobulin domains of Down syndrome cell adhesion molecule 1

Acta Crystallographica Section F Structural Biology Communications ◽

10.1107/s2053230x15008201 ◽

2015 ◽

Vol 71 (6) ◽

pp. 775-778 ◽

Cited By ~ 1

Author(s):

Linna Cheng ◽

Shu-Ang Li ◽

Yamei Yu ◽

Qiang Chen

Keyword(s):

Down Syndrome ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Rna Splicing ◽

Cell Adhesion Molecule ◽

Crystallographic Analysis ◽

Homophilic Binding ◽

Ig Superfamily ◽

Cell Adhesion Molecule 1 ◽

Insight Into

Down syndrome cell adhesion molecule 1 (Dscam1), a member of the immunoglobulin (Ig) superfamily, plays important roles in both the nervous and the immune systems. Via alternative RNA splicing,DrosophilaDscam1 encodes a vast family of Ig-containing proteins that exhibit isoform-specific homophilic binding. Whether different Dscam1 isoforms adopt the same dimerization mode is under debate, and the detailed mechanism of Dscam1 specificity remains unclear. In this study, eight different isforms of Dscam1 Ig1–4 have been cloned, overexpressed, purified to homogeneity and crystallized. X-ray data were collected to 1.9–4.0 Å resolution. These structures will provide the opportunity to perform extensive structural comparisons of different Dscam1 isoforms and provide insight into its specificity.

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