N-glycosylation at the SynCAM (synaptic cell adhesion molecule) immunoglobulin interface modulates synaptic adhesion
Adam I Fogel1, Yue Li, Joanna Giza
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
The Journal of Biological Chemistry
|August 27, 2010
Summary
Site-specific N-glycosylation differentially regulates synaptic cell adhesion molecules (SynCAMs) 1 and 2. This post-translational modification impacts SynCAM binding and is crucial for synapse formation and function.
Area of Science:
- Neurobiology
- Molecular Biology
- Structural Biology
Background:
- Synaptic cell adhesion molecules (SynCAMs) are crucial for connecting pre- and postsynaptic membranes.
- Regulation of trans-synaptic interactions is key to synapse development.
- Previous work established SynCAMs 1 and 2 engage in homo- and heterophilic interactions to induce presynaptic terminals.
Purpose of the Study:
- To investigate the impact of site-specific N-glycosylation on SynCAM structure and adhesive function.
- To elucidate the role of N-glycans in regulating trans-synaptic interactions.
Main Methods:
- Crystallographic analysis of SynCAM 2 to identify N-glycosylation sites.
- Structural modeling of SynCAM 1 Ig1 domain.
- Mass spectrometry and mutational studies to characterize glycosylation.
- Functional assays to assess SynCAM adhesion and synapse induction.
Main Results:
- Identified an N-glycan at Asn(60) in SynCAM 2's Ig1 domain, reducing adhesion.
- Identified N-glycosylation sites Asn(70)/Asn(104) in SynCAM 1's Ig1 domain, flanking the binding interface.
- N-glycosylation of SynCAM 1 increased interactions, further enhanced by sialic acid modification.
- N-glycosylation of SynCAM 1 promoted trans-synaptic interactions and was essential for synapse induction.
Conclusions:
- Site-specific N-glycosylation differentially modulates SynCAM binding interfaces.
- N-glycosylation acts as a post-translational mechanism to regulate trans-synaptic adhesion.
- This modification is critical for SynCAM-mediated synapse organization and function.
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