Structure of cell–cell adhesion mediated by the Down syndrome cell adhesion molecule

2021 ◽  
Vol 118 (39) ◽  
pp. e2022442118
Author(s):  
Luqiang Guo ◽  
Yichun Wu ◽  
Haishuang Chang ◽  
Ze Zhang ◽  
Hua Tang ◽  
...  
Keyword(s):  
Neural Network ◽  
Down Syndrome ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Neural Development ◽  
Cell Adhesion Molecule ◽  
Network Formation ◽  
Electron Tomography ◽  
Three Dimensional ◽  
Immunoglobulin Superfamily

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.

scholarly journals Architecture of cell–cell adhesion mediated by sidekicks

2018 ◽  
Vol 115 (37) ◽  
pp. 9246-9251 ◽  
Author(s):  
Hua Tang ◽  
Haishuang Chang ◽  
Yue Dong ◽  
Luqiang Guo ◽  
Xiangyi Shi ◽  
...  
Keyword(s):  
Neural Network ◽  
Cell Adhesion ◽  
Cell Growth ◽  
Adhesion Molecules ◽  
Neural Development ◽  
Cell Adhesion Molecules ◽  
Cell Adhesion Molecule ◽  
Network Formation ◽  
Electron Tomography ◽  
Cell Cell

Cell–cell adhesion is important for cell growth, tissue development, and neural network formation. Structures of cell adhesion molecules have been widely studied by crystallography, revealing the molecular details of adhesion interfaces. However, due to technical limitations, the overall structure and organization of adhesion molecules at cell adhesion interfaces has not been fully investigated. Here, we combine electron microscopy and other biophysical methods to characterize the structure of cell–cell adhesion mediated by the cell adhesion molecule Sidekick (Sidekick-1 and Sidekick-2) and obtain 3D views of the Sidekick-mediated adhesion interfaces as well as the organization of Sidekick molecules between cell membranes by electron tomography. The results suggest that the Ig-like domains and the fibronectin III (FnIII) domains of Sidekicks play different roles in cell adhesion. The Ig-like domains mediate the homophilic transinteractions bridging adjacent cells, while the FnIII domains interact with membranes, resulting in a tight adhesion interface between cells that may contribute to the specificity and plasticity of cell–cell contacts during cell growth and neural development.

Homophilic synaptic target recognition mediated by immunoglobulin-like cell adhesion molecule Fasciclin III

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4143-4152 ◽  
Author(s):  
H. Kose ◽  
D. Rose ◽  
X. Zhu ◽  
A. Chiba
Keyword(s):  
Neural Network ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Growth Cone ◽  
Cell Adhesion Molecule ◽  
Network Formation ◽  
Target Recognition ◽  
Basic Mechanism ◽  
Growth Cones ◽  
Homophilic Interaction

We demonstrate that the cell adhesion molecule Fasciclin III (FAS3) mediates synaptic target recognition through homophilic interaction. FAS3 is expressed by the RP3 motoneuron and its target muscles during synaptic target recognition. The RP3 growth cone can form synapses on muscles that ectopically express FAS3. This mistargeting is dependent on FAS3 expression in the motoneurons. In addition, when the FAS3-negative aCC and SNa motoneuron growth cones ectopically express FAS3, they gain the ability to recognize FAS3-expressing muscles as alternative targets. We propose that homophilic synaptic target recognition serves as a basic mechanism of neural network formation.

scholarly journals Down syndrome cell adhesion molecule and its functions in neural development

2011 ◽  
Vol 27 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Kun Zhu ◽  
Yiliang Xu ◽  
Jianghong Liu ◽  
Qi Xu ◽  
Haihong Ye
Keyword(s):  
Down Syndrome ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Neural Development ◽  
Cell Adhesion Molecule

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

2019 ◽  
Vol 294 (44) ◽  
pp. 16440-16450 ◽  
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

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

2018 ◽  
Vol 49 (11) ◽  
pp. 3638-3646 ◽  
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

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

2015 ◽  
Vol 71 (6) ◽  
pp. 775-778 ◽  
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.

Axonal cell-adhesion molecule L1 in CNS myelination

2004 ◽  
Vol 1 (1) ◽  
pp. 65-72 ◽  
Author(s):  
G. BARBIN ◽  
M.S. AIGROT ◽  
P. CHARLES ◽  
A. FOUCHER ◽  
M. GRUMET ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Culture Medium ◽  
Immunoglobulin Superfamily ◽  
Map Kinase Pathway ◽  
Cell Adhesion Molecule L1 ◽  
Cns Myelination ◽  
Kinase Pathway

Of the axonal signals influencing myelination, adhesion molecules expressed at the axonal surface are strong candidates to mediate interactions between myelinating cells and axons. The recognition cell-adhesion molecule L1, a member of the immunoglobulin superfamily has been shown to play important roles in neuronal migration and survival, and in PNS myelination. We have investigated the role of axonally expressed L1 in CNS myelination. In co-cultures of myelinating oligodendrocytes and neurons derived from murine brain, we demonstrate that, before myelination, L1 immunoreactivity is confined to neurites. After myelination commences, L1 expression is downregulated on myelinated axons and adjacent, but not yet myelinated, internodes. Interfering with L1 before the onset of myelination, by adding either anti-L1 antibody or L1-Fc fusion proteins to the culture medium, inhibits myelination. In addition, in purified cultures of oligodendrocytes, L1-Fc fusion protein prevents lysophosphatidic acid-induced activation of the mitogen-activated kinase (MAP)-kinase pathway. Together, our data indicate that L1 is involved in the initiation of CNS myelination, and that this effect might involve the dephosphorylation of oligodendroglial phosphoproteins.

scholarly journals Direct and Regulated Interaction of Integrin αEβ7 with E-Cadherin

1998 ◽  
Vol 140 (1) ◽  
pp. 197-210 ◽  
Author(s):  
Jonathan M.G. Higgins ◽  
Didier A. Mandlebrot ◽  
Sunil K. Shaw ◽  
Gary J. Russell ◽  
Elizabeth A. Murphy ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Fusion Protein ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Divalent Cations ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Vital Role ◽  
Immunoglobulin Superfamily ◽  
E Cadherin

The cadherins are a family of homophilic adhesion molecules that play a vital role in the formation of cellular junctions and in tissue morphogenesis. Members of the integrin family are also involved in cell to cell adhesion, but bind heterophilically to immunoglobulin superfamily molecules such as intracellular adhesion molecule (ICAM)–1, vascular cell adhesion molecule (VCAM)–1, or mucosal addressin cell adhesion molecule (MadCAM)–1. Recently, an interaction between epithelial (E-) cadherin and the mucosal lymphocyte integrin, αEβ7, has been proposed. Here, we demonstrate that a human E-cadherin–Fc fusion protein binds directly to soluble recombinant αEβ7, and to αEβ7 solubilized from intraepithelial T lymphocytes. Furthermore, intraepithelial lymphocytes or transfected JY′ cells expressing the αEβ7 integrin adhere strongly to purified E-cadherin–Fc coated on plastic, and the adhesion can be inhibited by antibodies to αEβ7 or E-cadherin. The binding of αEβ7 integrin to cadherins is selective since cell adhesion to P-cadherin–Fc through αEβ7 requires >100-fold more fusion protein than to E-cadherin–Fc. Although the structure of the αE-chain is unique among integrins, the avidity of αEβ7 for E-cadherin can be regulated by divalent cations or phorbol myristate acetate. Cross-linking of the T cell receptor complex on intraepithelial lymphocytes increases the avidity of αEβ7 for E-cadherin, and may provide a mechanism for the adherence and activation of lymphocytes within the epithelium in the presence of specific foreign antigen. Thus, despite its dissimilarity to known integrin ligands, the specific molecular interaction demonstrated here indicates that E-cadherin is a direct counter receptor for the αEβ7 integrin.

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